Report 2015 - Mobi4Health

Transkrypt

Research Progress
Report 2015
Intercollegiate Faculty of Biotechnology
of University of Gdańsk and Medical University of Gdańsk
Antoniego Abrahama 58, 80-307 Gdańsk, Poland
www.biotech.ug.edu.pl
2016
Published by
Intercollegiate Faculty of Biotechnology
of University of Gdańsk and Medical University of Gdańsk
Executive Editor
Prof. Igor Konieczny, PhD
Coordination
Prof. Andrzej C. Składanowski, PhD
Katarzyna Maczyszyn
Izabela Raszczyk
Layout & Design
Katarzyna Maczyszyn
Research Group Profiles & Core Facility Descriptions
Courtesy of the respective Research Groups and Core Facilities
Text and Edition
Dean’s Office for Research and Project Management
MOBI4Health project has received funding from the European
Union’s Seventh Framework Programme for research,
technological development and demonstration under grant
agreement no. 316094 and from the Ministry of Science and
Higher Education.
Contents
A Word from the Dean
5
IFB Authorities (2012-2016)
7
IFB International Scientific Advisory Board
8
IFB Consulting Board
8
ABOUT IFB
9
Structure of IFB
10
Background
12
Achievements
12
Research Potential
13
Research Projects
14
Ministry of Science and Higher Education
14
IFB Publications 2011-2015
15
Major Investments in 2012-2015
15
Number of Research Grants Obtained in 2012-2015
15
Funding for Research Grants Obtained in 2012-2015
16
IFB Budget in 2012 - 2015
16
Structure of IFB Budget 2015
16
Facilities and Equipment
17
New Building
19
Strategic Partnerships
20
Invited lectures in 2015
21
Teaching Activities and Programmes
22
Biotechnology Summer Schools
24
MOBI4Health
27
FP7 Project MOBI4Health
28
Cooperation with European Partners
29
MOBI4Health Project Progress in 2015
30
RESEARCH GROUP PROFILES
33
Laboratory of Biologically Active Compounds
34
Laboratory of Biological Plant Protection
36
Laboratory of Biomolecular Systems Simulations
38
Laboratory of Biophysics
40
Laboratory of Biopolimer Structure
42
Laboratory of Cell Biology
44
Laboratory of Evolutionary Biochemistry
46
Laboratory of Molecular Bacteriology
48
Laboratory of Molecular Biology
50
Laboratory of Molecular Diagnostics
52
Laboratory of Molecular Enzymology
54
Laboratory of Physical Biochemistry
56
Laboratory of Plant Biochemistry
58
Laboratory of Plant Protection and Biotechnology
60
Laboratory of Protein Biochemistry
62
Laboratory of Recombinant Vaccines
64
Laboratory of Virus Molecular Biology
66
Recent Publications
68
Important Dates and Facts
79
A Word from the Dean
A unique environment for interdisciplinary research in Life Sciences
The Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk
(IFB) creates a unique environment for conducting interdisciplinary research and teaching in the
area of medical biology, molecular biology and molecular biotechnology. As the only intercollegiate
faculty in Poland, we use the infrastructure and expertise provided by two universities and follow our
goal of combining the best international standards of research with the highest quality of teaching.
International programs and collaboration with international strategic partners has facilitated the
introduction of new research methods and combining research areas.
Year 2016 is important in terms of further development of our potential. We will benefit from
finishing EU REGPOT project MOBI4Health and educational programs which boost our research,
innovation and teaching capacities. Year 2016 it is also the year of starting EU Horizon 2020
STARBIOS 2 project. With 11 European partners we will cooperate in the field of structural transformation to attain responsible BIO Sciences. Moreover, we are just after a relocation to a completely new
research complex in the University main campus in Oliva. It is a unique opportunity for the
improvement of organization of research and teaching. It opens new possibilities and perspectives but
especially at the beginning requires hard work to set up things properly. Due to recent investments
we will continue the development of IFB core facilities. Also, international cooperation will be
continued. Focusing on fields of our expertise in molecular microbiology, medical biology, molecular
diagnostics and molecular plant biology will result with biotechnological applications for health and
life quality. It is consistent with one of main priorities in the EU Horizon 2020, Polish national strategy
and recently defined Pomeranian Region Smart Specialization.
It is our vision to expand research and teaching potential as well as intensify and widen our
partnerships with research institutions and industry in Europe and world-wide. We warmly invite you
to cooperation in the area of biotechnology – as our student, research partner or business partner.
March 2016
Prof. Igor Konieczny
Dean of IFB UG&MUG
INTERCOLLEGIATE FACULTY OF BIOTECHNOLOGY OF UNIVERSITY OF GDAŃSK AND MEDICAL UNIVERSITY OF GDAŃSK
5
Intercollegiate Faculty of Biotechnology of University
of Gdańsk and Medical University of Gdańsk (IFB)
IFB Authorities (2012-2016)
Dean
Deputy Dean for Student Affairs & Education
Prof. Sylwia Jafra
Deputy Dean for Science
Prof. Michał Obuchowski
Deputy Dean for Development
Prof. Stanisław Ołdziej
7
IFB International Scientific Advisory Board
In 2015 IFB decided to establish the IFB International Scientific Advisory Board. By the Polish law,
IFB as a research & teaching institution is evaluated every four years by two different governmental
committees. An international advisory panel is therefore not an obligation. However, it is a part of
IFB’s capacity building strategy in order to obtain advice from prominent scientists from different
fields covering research topics conducted at IFB. The nominations to the IFB International Scientific
Advisory Board were based on the experts’ research excellence, management experience and broad
research expertise. These aspects are important to cover a broad spectrum of research work and
other research-related activities at IFB and provide recommendations for further actions.
Members of the IFB International Scientific Advisory Board:
Prof. Burkhard Brandt - Universitätsklinikum Schleswig Holstein, Institut für Klinische Chemie Kiel
Prof. Bernd Bukau - Universität Heidelberg Center for Molecular Biology (ZMBH)
Prof. Maarten Koornneef - Max Planck Institute for Plant Breeding Research
Prof. Arvind H. Patel - MRC-University of Glasgow Centre for Virus Research,
Prof. Dan Tawfik - Weizmann Institute of Science
IFB Consulting Board
IFB Consulting Board supports the planning of the development of the Faculty, in particular
the new paths of teaching programmes. Members of the Consulting Board are companies and
institutions from the biotechnology sector.
The main goal of cooperation is increasing the quality of teaching and ensuring a dynamic start at
job market for our graduates. The Consulting Board evaluates study courses offered at IFB from
a business and employers perspective and gives recommendations. This practice has already proved
to be successful, since IFB has received the award of The Best Faculty of Studies and a distinction for
the set of learning outcomes prepared for the specialty of Biotechnology as a model set.
Members of IFB Consulting Board are representatives of companies and institutions such as:
Adamed
A&A Biotechnology
Biofaktor
Gdański Park Naukowo-Technologiczny
Grupa LOTOS
Instytut Biotechnologii i Antybiotyków
J.S. Hamilton Poland S.A.
KAWA.SKA Sp. z o.o.
Krzysztof Kucharczyk Techniki Elektroforetyczne Sp. z o.o.
M+W Process Industries Sp. z o.o.
Ośrodek Salmonella „IMMUNOLAB” Sp. z o.o.
Polpharma Biologics
Polpharma SA
Przedsiębiorstwo Innowacyjno-Wdrożeniowe IMPULS
I Akademickie Liceum Ogólnokształcące
8
ABOUT IFB
Structure of IFB
University of Gdańsk, Institute of Biotechnology
Institute of Biotechnology
Prof. Bogdan Banecki, Director of the Institute of Biotechnology
Wojciech Śledź PhD, Deputy-Director of the Institute of Biotechnology
Department of Biotechnology, Head: Prof. Ewa Łojkowska
Laboratory of Plant Protection and Biotechnology, Head: Prof. Ewa Łojkowska
Laboratory of Molecular Diagnostics, Head: Prof. Krzysztof Bielawski
Laboratory of Plant Biochemistry, Head: Prof. Antoni Banaś
Laboratory of Biological Plant Protection, Head: Prof. Sylwia Jafra
Laboratory of Biologically Active Compounds, Head: Prof. Aleksandra Królicka
Department of Molecular and Cellular Biology, Head: Prof. Krzysztof Liberek
Laboratory of Protein Biochemistry, Head: Prof. Krzysztof Liberek
Laboratory of Molecular Biology, Head: Prof. Igor Konieczny
Laboratory of Evolutionary Biochemistry, Head: Prof. Jarosław Marszałek
Laboratory of Physical Biochemistry, Head: Prof. Bogdan Banecki
Laboratory of Biophysics, Head: Prof. Jacek Piosik
Laboratory of Biopolymers Structure, Head: Prof. Stanisław Ołdziej
Laboratory of Biomolecular Systems Simulation, Head: Prof. Rajmund Kaźmierkiewicz
Laboratory of Virus Molecular Biology, Head: Prof. Krystyna Bieńkowska-Szewczyk
Laboratory of Recombinant Vaccines, Head: Prof. Boguław Szewczyk
Medical University of Gdańsk
Department of Medical Biotechnology, Head: Prof. Jacek Bigda
Laboratory of Cell Biology, Head: Prof. Jacek Bigda
Laboratory of Molecular Enzymology, Head: Prof. Andrzej C. Składanowski
Laboratory of Molecular Bacteriology, Head: Prof. Michał Obuchowski
Core Facility Laboratories, Head: Prof. Michał Obuchowski
Teaching Laboratories, Head: Prof. Sylwia Jafra
Dean’s Office for Student Affairs, Head: Ewa Brzana
Dean’s Office for Research and Project Management, Head: Anna Gwizdek-Wiśniewska, PhD
10
Structure of IFB
University of Gdańsk (UG)
Medical University of Gdańsk (MUG)
Rector
Senate
Rector
Senate
IFB Faculty Council
Dean of IFB
Dean’s Office for Student Affairs & Educaon
Vice-Dean for Teaching
and Student Affairs
Dean’s Office for Research and Project Managment
Vice-Dean for Development
Vice-Dean for Science
lnstute of Biotechnology, UG
Director of the lnstute
Deputy Director
Department of Biotechnology
Laboratory of Plant Protecon and Biotechnology
Laboratory of Molecular Diagnosc
Laboratory of Biological Plant Protecon
Laboratory of Biologically Acve Compounds
Teaching
Laboratories
Department of Molecular and Cellular Biology
Laboratory of Evoluonary Biochemistry
Core Facility
Laboratories
Laboratory of Biopolymers Structure
Laboratory of Biomolecular Systems Simulaon
Department of Medical Biotechnology, MUG
11
Background
The Intercollegiate Faculty of Biotechnology of the University of Gdańsk and the Medical University of
Gdańsk (IFB) has been established in 1993 by the decision of the Senates of the University of Gdańsk
(UG) and the Medical University of Gdańsk (MUG). The initiators of the Faculty were Prof. Karol Taylor,
Prof. Anna Podhajska and Prof. Wacław Szybalski. The Faculty is a unique institution in Poland created by
two universities. This leads to the interdisciplinary character of the conducted research and teaching by
combining biomedical and bio-molecular issues and their applications in biotechnology for health and
life quality. Since 1999, IFB is authorized to confer the degree of doctor, and since 2010 - the scientific
degree of habilitated doctor in the area of biological sciences - discipline of biochemistry. Taking into
account PhD students, approximately 193 people take part in research and teaching at IFB.
Achievements
IFB is a leading research and teaching institution that since 2002 has had the status of the European
Centre of Excellence in Biosafety and Molecular Biomedicine (since EU FP5) and occupies high
positions in the rankings of the Ministry of Science and Higher Education regarding scientific
effectiveness. In 2013, in a parametric assessment IFB was granted category A and earned the third
place in Poland.
The quality of teaching at IFB is evaluated as the highest in Poland. The Polish Accreditation
Committee awarded the Faculty with a distinction for the quality of teaching (2011) and the Ministry
of Science and Higher Education granted the specialty of BIOTECHNOLOGY at IFB the title of The Best
Major (2012). The Central Council of Science and Higher Education recognised the set of learning
outcomes prepared by IFB for the specialty of Biotechnology as a model one. These are the only
distinctions of this kind granted in Poland in the area of biological sciences.
Faculty members play important functions in international societies and scientific commissions,
for example Prof. Krzysztof Liberek is a member of EMBO, Prof. Igor Konieczny - member of the
Commission of European Cooperation in Science and Technology (COST), Prof. Krzysztof
Bielawski - vice-president of ScanBalt and Council Member of the European Society for
Translational Antiviral Research (ESAR), Prof. Ewa Łojkowska – member of the International Selection Committee of the Award L’OREAL-UNESCO For Women in Science International Rising Talents
and Prof. Bogusław Szewczyk - member of the Commission of European Food Safety Authority.
IFB staff members are also laureates of prestigious programmes and awards, including awards for
young scientists (EMBO YIP, HHMI, Polish national programmes such as: LIDER, InnoDoktorant, TOP
500 Innovators, MISTRZ, START, HOMING PLUS). Publications by IFB staff have received numerous
awards and distinctions for the best work conducted in Polish laboratories, granted by the Committee
of Microbiology of Polish Academy of Science, Polish Genetic Society or Polish Biochemical Society.
12
Research Potential
IFB comprises 17 teams involved in research activities. Basic as well as applied research
areas at IFB cover molecular microbiology, medical biology and molecular diagnostics,
and molecular plant biology. These areas are the basis of biotechnology development.
Relationships and synergy between these research areas give an added value in the form
of common thematic areas. Maintaining three main research areas increases the number
of interactions between research teams, their effectiveness and broadens competence.
At IFB about 60 research pathways supported by external grants are conducted simultaneously.
28 projects concern molecular microbiology. In these projects various microorganisms are used as
models for the analysis of basic cell processes. The main research topics include protein aggregation and
disaggregation, the role of molecular chaperones, proteolysis, replication of DNA, plant, animal and
human pathogens, infection mechanisms, cell response to viral infections and pathogen diagnostics.
30 projects concern the area of medical biology and molecular diagnostics. We conduct work
concerning recombinant vaccines, edible vaccines, new immune-modulating substances development, proteases inhibitors in anticancer therapy, tumor markers, neoplasm analysis in in vivo models,
markers used in neurodegenerative diseases diagnostics, nanobiotechnology in treating burns as well
as diagnostic methods in infectious plant diseases.
Another research area concerning molecular plant research is connected with the already mentioned research projects concerning the diagnostics of plant diseases, projects related to
infection mechanisms and identification of genes and lipid metabolic pathways in plant cells.
Research is also carried out into identification of plant nutraceutics.
13
Research Projects
Selected research grants 2013/2015
Project
Project Leader
Start
Funding
Source*
Programme
EUR
Molecular mechanisms of chaperones in protein disaggregation
Prof. Krzysztof Liberek
2013
NSC
MAESTRO
678.000
Molecular mechanisms behind functional diversification
of mitochondrial Hsp70 chaperones
Prof. Jarosław Marszałek
2013
NSC
MAESTRO
632.000
Host factors in hepatitis B virus cccDNA formation as novel antiviral targets and biomarkers - identification, preclinical evaluation and impact for liver disease (hepBccc)
Prof. Krzysztof P. Bielawski
2014
NCRD
Infect-ERA
292.000
The application of pangenome-based approach to
identify genes responsible for adaptation of pectinolytic
bacteria - Dickeya solani and Pectobacterium wasabiae
to causing disease symptoms on potato under temperate
climate conditions.
Prof. Ewa Łojkowska
2015
NCN
Harmonia
291.000
Oral vaccine against influenza virus for poultry
Dawid Nidzworski, Phd
2013
NCRD
LIDER
286.000
The combined (synergistic) use of the lytic bacteriophages and antagonistic bacterial isolates in the biological
control of pectinolytic bacteria Pectobacterium spp. and
Dickeya spp. on potato (Solanum tuberosum L.)
Robert Czajkowski, Phd
2015
NCRD
LIDER
284.000
283.000
Centre of biotechnology of medical products. A series of
innovative biopharmaceuticals for therapy and prophylactics of humans and animals
Prof. Bogusław Szewczyk
2014
NCRD
Operational
Programme
Innovative
Economy
Increasing the efficacy of breast cancer therapy with the
use of new MAPK/ERK kinase inhibitors
Anna Kawiak, Phd
2013
NCRD
LIDER
225.000
Vaccine against influenza A – innovative production of
antigenic subunits
2014
NCRD
Applied
Research
Programme
210.000
The role of iron- and oxoglutarate-dependent dioxygenases in Arabidopsis thaliana responses to environmental
stresses and regulation of iron homeostasis
Anna Ihnatowicz, PhD
2015
NCN
Opus
202.000
Mechanism of action of GerA receptor in B. subtilis
spores
2015
NCN
Harmonia
197.000
Characteristic of the crucial mechanisms involved in
the pathogenicity of Dickeya solani – regulation of the
expression of gens coding virulence factors
2013
NSC
Harmonia
167.000
Experimental and clinical study of CD151-regulated activity of FGFR2 in breast cancer progression
Rafał Sądej, Phd
2013
NSC
Harmonia
158.000
Factors involved in antibacterial activity of Pseudomonas
sp. P482 strain against plant pathogenic bacteria from
Dicekya and Pectobacterium genera
Prof. Sylwia Jafra
2013
NSC
Opus
109.000
Biochemical, functional and immunological properties of
new recombinant envelope glycoproteins and virus-like
particles of hepatitis C virus
Katarzyna Grzyb, Phd
2013
NSC
Sonata
102.000
Improving anti-virus neutralizing antibodies
Krzysztof Lacek, Phd
2013
MSHE
IUVENTUS
PLUS
94.000
Functionalization of photosensitizing compounds with
antimicrobial peptides to enhance photoantimicrobial
chemotherapy (PACT)
Joanna Nakonieczna,
Phd
2014
NSC
Opus
80.000
Identification,characterization and phylogenetic analysis
of genes specifically up-regulated in “Dickeya solani”
(biovar 3 Dickeya spp.) and Pectobacterium atrosepticum
at different growth temperatures
Robert Czajkowski, Phd
2013
MSHE
IUVENTUS
PLUS
70.000
Dawid Nidzworski, Phd
2013
NCRD
PATENT PLUS
64.000
International patent protection of invention „A method of
fabrication of an immunosensor and its use for detection
of influenza virus” (P-399993) and study of commercialization process
MSHE – Ministry of Science and Higher Education
NSC
– National Science Centre
NCRD – National Centre for Research and Development
14
IFB Publications 2011-2015
Scientific journals quality classification into quadrilles according to Journal Citation Reports – Tomson Reuters
Major Investments in 2012-2015
Number of Research Grants Obtained in 2012-2015
15
Funding for Research Grants Obtained in 2012-2015
IFB Budget in 2012 - 2015
Structure of IFB Budget 2015
without structural funds
16
Facilities and Equipment
The facilities of IFB comprise laboratories of the Institute of Biotechnology,
University of Gdańsk, as well as facilities at the Medical University of
Gdańsk campus.
In 2011, we decided to set up core facility laboratories in which a wide
range of methods will be implemented, allowing to analyse interactions
among proteins, proteins and nucleic acids, proteomic analyses, lipid
analyses, post-translational modifications as well as molecular diagnostics.
Core Facility Laboratories comprise several modules.
▪ Laboratory of Biomolecular Analysis
This laboratory allows insight into molecular structure and interactions
within biological systems. It is already equipped with spectro- and
fluorometers, e.g. JASCO FP-8500, microplates reader, plasmon
resonance analyser Biacore 2000, anaerobic chamber (COY Lab Products),
ultracentrifuge Beckman L55, Atomic Force Microscope BioScope Resolve
with scanning head MultiMode8 Lockout Specs (Bruker) and apparatus for
microscale thermophoresis Monolith NT.115 (NanoTemper Technologies).
▪ Laboratory of Mass Spectrometry
This unit has been established within the FP7 project MOBI4Health.
We have four distinct spectrometers providing various applications, for
instance in genomics, transcriptomics, proteomics, lipidomics
(MassARRAY® Analyzer 4; MALDI-TOF/TOF™ 5800 with MALDI Imaging,
QTRAP® 6500 LC/MS/MS, TripleTOF® 5600). Mass spectrometry specialists
facilitate research work in the MS Laboratory.
▪ Laboratory of Genetic Analysis
Here, the equipment comprises new genetic analysis devices (real-time
thermocycler Light Cycler 480, real time cell analyser xCELLigence DP,
homogeniser MagnaLyser, aparatus for the automatic isolation of nucleic
acids MagnaPure 2.0, apparatus for nucleic acids capillary electrophoresis Tape Station 2200 and automatic pipetting station epMotion 5070).
This laboratory is also equipped with advance plate reader EnVision
Multilabel Reader (Perkin-Elmer).
▪ Laboratory of Imaging and Data Analysis
IFB has three confocal microscopes (Nikon PCM-2000, Leica DMI6000 CS
SP8 and microscope Leica HCS LSI) as well as several fluorescent ones.
The confocal microscope Leica TCS SP8 is equipped with white light
laser, which perfectly matches the excitation wavelength ranging
between 470 and 670nm of any fluorophore. Up to eight excitation lines can
be used - simultaneously. This microscope is equipped with five spectral
detectors (350-800nm) working independently. Leica TCS LSI macro
confocal is the first super zoom confocal that offers high resolution plus
a large 16x16mm field of view for in vivo imaging. Both Leica microscopes
are equipped with a special incubation chamber for Live cell imaging.
Nikon PCM 2000 fluorescent confocal microscope equipped with 3 lasers
and ultra-sensitive colorcamera Hamamatsu.
▪ Laboratory of In Vitro Plant Cultures
The infrastructure consists of several growth chambers that serve as
a controlled environment for the growth of in vitro cultured plants.
The growth chambers contain various in vitro cultured endangered plants
17
(e.g. Droseracae and Orchidaceae species), hairy root cultures, plants
containing bioactive compounds and GM plants. These cultures are used
for breeding and reintroduction purposes, transformations as well as for
obtaining biologically active secondary metabolites.
▪ Isotope Laboratory Type III
The laboratory comprises full equipment indispensable for conducting research with radioisotopes such as 3H, 14C, 32P, 33P and 35S.
The scintillation counter is available in the laboratory.
▪ Laboratory for Higly Infectious Pathogens
The IFB core facility established of Institute Biotechnology possesses
also two laboratories in Biosafety Level 3 (BSL3) which are designed for
working with dangerous animal virsues and bacterial pathogens
(for example influenza virus or Mycobacterium tuberculosis).
Both laboratories allow safe manipulation with such pathogens and are
equipped with laminar chamber class III and several laminar chambers
class II. The safety of work is achieved by a stricty controlled access to the
lab as well as by a multistep pressure barrier between the working space
and rest of the building.
The Core Facilities are available for Faculty members, research groups
from other Faculties at the University of Gdańsk and Medical University
of Gdańsk as well as for external users form other scientific institutes as
well as commercial institutions.
In 2015 we have upgraded our equipment investing approx. 600 000 EUR.
In future we plan to increase our capabilities by obtaining a microscope
equipped with STED system, flow cytometry apparatus with imaging
system, cell sorter and CD spectrometer.
18
New Building
At the end of 2015 the new building of the Institute of Biotechnology
has been completed. The building is situated on the Baltic Campus of the
University of Gdańsk. The construction took less than two years.
This investment received a 15 million EUR funding from the Operational
Programme Infrastructure and Environment within Structural Funding
of the EU.
The building is a modern research-teaching complex. The usable area
is 7 868.18 m² and covers 4 floors and a basement level with laboratories
and fitotrons.
It includes a specialized core facility zone, an area of research laboratories,
seminar rooms, computer rooms, an auditory for 180 people, rooms
for our Student Scientific Association, a reading room, a room for the
Faculty Council, new technical systems (audio-visual systems, access control
systems etc.).
19
Strategic Partnerships
The strategic partners of the Faculty comprise the International Institute of Molecular and Cell
Biology (IIMCB) from Warsaw, an international network of research institutions within the FP7
project MOBI4Health and the association ScanBalt BioRegions.
In collaboration with International Institute of Molecular
and Cellular Biology (IIMCB), IFB created a consortium for
cooperation in the area of research and modern teaching
(2012). We have jointly running Life Science Mathematics
Interdisciplinary Doctoral Studies (LiSMIDoS) and we are
also partners in the project Polish Roadmap for Research
Infrastructures.
Our second strategic partner is the international network
of research centres, created on our own initiative within
the framework of the FP7 project MOBI4Health, the
‘Center of Molecular Biotechnology for Healthy Life–Biotech
solutions bringing health to living organisms and environment
supported by mass spec-focused research platform’.
1.5 million EUR have been dedicated to establishing of the
most modern mass spectrometry laboratory, while the
remaining funds in the amount of approx. further 3 million
EUR have been planned to support the the potential of the
scientific staff, including international cooperation.
European partners in this network are:
Universitet Konstanz, Germany
University of Nottingham, UK
Centro de Investigaciones Biologicas, Madrid, Spain
Institute National de Sciences Apliquees (INSA) Lyon, France
INSERM, Institute National de la Sante et de la Recherche
Medicale, Lyon, France
Federico II University of Naples, Italy
Philipps Universitet Marburg, Germany
Georg-August-Universitet Gottingen, Germany
Laboratory Agronomy & Environment ENSAIA-INPL,
Nancy, France
FORTH Biomedical Research Institute, Ioannina, Greece
The third strategic partner is the ScanBalt Association,
comprising 60 universities and over 2 000 firms from the
biotechnology sector of the Baltic Sea Region.
The Vice-Chairman of the association is our Faculty
member - Prof. Krzysztof Bielawski, who continues the work of
Prof. Ewa Łojkowska, Dean of IFB in 2005-2012, Vice-Chairwoman of ScanBalt in 2010-2014. In the framework of ScanBalt,
we are members of the ScanBalt Campus network; we jointly prepared the ScanBalt educational platform and also (co-)
organised in Gdańsk the conferences ScanBalt Forum 2003 and
ScanBalt Forum 2013 as well as Biotechnology Summer Schools.
20
Invited lectures in 2015
1.
Danuta Gutowska-Owsiak , PhD - Filaggrin utilize actins to regulate keratinocyte differentiation and
cornification during epidermal barrier formation
2.
Mikhail I. Zarayskiy (Clinical Laboratory, First Pavlov State Medical University of Saint
Petersburg, Russia) - The modern concept of the DNA structure and regulation
3.
Luis M. Schang, PhD (Li Ka Shing Institute of Virology, University of Alberta, Canada)
Chromatin silencing as an antiviral innate immune response
4.
Paul Williams (Centre for Biomolecular Sciences, University of Nottingham, United Kingdom)
The art of antibacterial warfare – deception through interference with quorum sensing–mediated
communication
5.
Pierre Savatier (INSERM U846 Stem Cell and Brain Research Institute, France)
Understanding and manipulating pluripotent stem cells: toward applications in basic biology, biotechnology and medicine
6.
Ezio Ricca (University of Naples Federico
II, Italy)
Microbiology and Biotechnological
Applications of Spore Formers
7.
Adam Jagiełło Rusiłowski (University of Gdańsk, Poland) Principles of intercultural cooperation
for research teams
8.
Florian Hollfelder (University of Cambridge, United Kingdom) Rules and Tools for Efficient Enzyme
Evolution, Recruitment and Discovery
9.
Rafael Giraldo (Centro de Investigaciones Biológicas – CSIC, Madrid, Spain)
Synthetic Biology: News ways and tools to engineer biological systems
10.
Filip Dutka (Institute of Physical Chemistry, Polish Academy of Sciences, Poland)
Growth of microorganisms in microfluidic devices
11.
Charles Cantor (Sequenom Inc., San Diego, California, USA) The future of DNA diagnostics
12.
Zbigniew Brzózka (Warsaw University of Technology, Poland)
Lab-on-a-Chip devices for long-term cell culture and anticancer drug activity evaluation
13.
Zbigniew Arent DVM, PhD, MRCVS Aspects of immunity in bovine leptospirosis
14.
Frank Graage (Steinbeis-Forschungszentrum Technologie-Management Nordost, Germany)
Motivation to get engaged with Horizon 2020 for scientists.
15.
Niki Karachaliou, PhD (Catalan Institute of Oncology (ICO) – Badalona, Barcelona, Spain)
Integrated research in STAT3 in cancer stem cells. Early adaptive resistance to EGFR inhibition
in EGFR mutant Non-Small-Cell-Lung-Cancer
16.
Peter Gimeson (Malvern Instruments Ltd.) Managing heat and disorder, calorimetric
assays in life sciences
17.
Tim Maisch, PhD (University Hospital Regensburg, Germany) A new trend against Superbugs:
The Photodynamic Principl
18.
Alessio Mengoni (University of Florence, Italy)
Principles of genome analysis and comparative bacterial genomics
19.
Monika Słomińska-Wojewódzka, PhD (University of Gdańsk, Poland) Substrate specificity of the
endoplasmic reticulum chaperone proteins EDEM1 and EDEM2.
21
Teaching Activities and Programmes
IFB runs BSc, MSc and PhD studies, educating over 365 students,
including 84 doctoral students. The research activity conducted at IFB is
interwoven with a teaching programme that includes an active involvement
of students in research. Thanks to the intercollegiate character of the
Faculty, all students, independently of the degree they study, use the
research and teaching infrastructure offered by both home universities,
the University of Gdańsk and the Medical University of Gdańsk.
Both the research and the educational programmes at the IFB have an
interdisciplinary character and are based on international cooperation. Our students have an opportunity to conduct their Master thesis
projects and carry out research internships in foreign institutions.
Classes of the second-cycle studies are conducted in English.
At present, BSc and MSc studies are run in cooperation with the University of
Houston Downtown, University of Chicago, Virginia State University in
the US. While designing teaching programmes, we are taking advantage
of our foreign partners’ experience and are implementing international
standards. For such activities, IFB has secured e.g. 150 000 EUR within
the project: “Internalisation of teaching through cooperation with the
University of Houston-Downtown”.
IFB has received 250 000 EUR funding from the Polish Ministry of
Science and Higher Education for the best study programmes and implemention of the most advanced concepts for improving the quality of
teaching (2012). IFB has also received funding in the amount of 250 000 EUR
from the Ministry for having obtained the A distinction for the quality of
teaching from the Polish Accreditation Committee.
We established an Advisory Board composed of representatives
of business and industry sector advising IFB on further development,
especially regarding the teaching programmes from the point of view
of potential employers.
IFB runs doctoral studies in the frame of the following programmes:
▪ Doctoral Studies in Chemistry and Biochemistry in cooperation with the
Faculty of Chemistry of UG;
▪ PhD studies ‘Life Sciences and Mathematics Interdisciplinary Doctoral
Studies (LiSMIDoS).
Annually, we organize a PhD Programme Reporting Session in form of
an open conference, where PhD students present the progress of their
research projects.
An integral element of teaching and developing young professionals is
the organisation of Biotechnology Summer Schools, held annually for
22 years. Lectures are delivered thee by outstanding lecturers,
invited from Poland and abroad, for instance the Nobel Prize laureate
Prof. Robert Huber. Co-organisers of Biotechnology Summer Schools
have been, among others, FEBS, Polish Academy of Science, Russian
Academy of Science, ScanBalt, Marie Curie Training Network, Foundation for
Polish Science.
22
23
Biotechnology Summer Schools
The main purpose of the Summer School project is to develop so
called‚ soft skills, such as teamworking, techniques of presentation and
autopresentation, time management.
About XXI Biotechnology Summer School
The XXI Biotechnology Summer School took place from 30 June to 4 July
2015 in Kadyny.
The topic of was Biotech Innovations and International Research
Cooperation. The aim of the conference was to promote knowledge
about the newest biotechnological achievements and build a scientific
network between students, PhD students and young scientists together
with experienced lecturers from the leading institutions from Poland
and from abroad. The Summer School had also the goal to improve
competences of young scientists in the area of science communication.
The participants took part in a workshop on scientific cooperation
and other workshops prepared by KAWA.SKA concerning microscopy.
Additional activities for participants have been prepared such as: integration field game, a team building workshop, regional trip through Kadyny
village and a traditional fancy dress party.
Organizers were
Angelika Michalak.
Prof.
Michał
Obuchowski,
Elżbieta
Moroz,
Speakers were Prof. Zbigniew Brzózka (Warsaw University of Technology, Poland), Joanna Bagniewska, PhD (University of Reading, United
Kingdom), Charles
Cantor, PhD (Sequenom Inc., San Diego,
California, USA), Arkadiusz Dorna (Enbio Technology Sp. z o.o., Poland), Filip
Dutka, PhD (Institute of Physical Chemistry, Polish Academy of Sciences,
Poland), Grzegorz Gacek (KAWA.SKA Sp. z o.o., Poland), prof. Rafael
Giraldo (Centro de Investigaciones Biologicas - CSIC, Madrid, Spain), Florian
Hollfelder, PhD (University of Cambridge, United Kingdom), Adam Jagiełło
Rusilowski, PhD (University of Gdansk, Poland), Jarosław Korczynski, PhD
(KAWA.SKA, Poland), Takashi Kuwana, PhD (KAWA.SKA Sp. z o.o.,
Poland), prof. Ezio Ricca (University of Naples Federico II, Italy), Pierre
Savatier, PhD (INSERM U846 Stem Cell and Brain Research Institute, France),
prof. Paul Williams (Centre for Biomolecular Sciences, University of
Nottingham, United Kingdom).
24
Brief history of Biotechnology Summer Schools
Biotechnology Summer Schools are organized annually since 1994.
The idea of Biotechnology Summer School (BSS) came from Professor
Anna J. Podhajska, who implied that students and young scientists
should actively participate in obtaining knowledge and establishing
contacts with scientists from all over the world, not only in formal
conditions but also outside the University. That is why the participants
of BSS are not only biotechnology students but also students in related
biological fields from Poland and from abroad, young scientists and even
advanced pupils interested in this topic.
Topics of BSS vary from year to year. Prof. Anna Podhajska gained many
people’s support over her initiative. The number of sponsors increased
every year and thanks to all these companies and institutions the
organization of Biotechnology Summer School has been possible.
Biotechnology Summer Schools were honored with the presence of many
eminent scientists such as professors: Ewa and Ernest Bartnik, Stanisław
Bielecki, Klaus Halhlbrock, Waleria Hryniewicz, Robert Huber (Nobel Prize
winner in Chemistry in 1988), Berndt Jastorf, Adam Jaworski, Roman
Kaliszan, Wladysław Kunicki Goldfinger, Andrzej Legocki, Janusz Limon,
Mirosław Matuszyński, Jerzy Paszkowski, Andrzej Płucienniczak, Richard
P. Sinden, Piotr Stępien, Wadaw Szybalski, Tomasz Twardowski, Jacques H.
Weil, Robert Wells, Brigitte Wittman-Liebold, Maciej Zenktler, Maciej Żylicz.
No less important than learning is having fun. Many entertaining
activities for Summer Schools are always planned. A fancy-dress party,
a bonfire with singing, field games, sports, playing on words, integrational
workshops are the part of every School. We also organize some visits in
local, historical places and regional trips.
25
CENTRE OF MOLECULAR BIOTECHNOLOGY
FOR HEALTHY LIFE
biotech solutions bringing health to living
organisms and environment supported
by mass spec-focused research platform
FP7 Project MOBI4Health
MOBI4Health: Centre of Molecular Biotechnology for Healthy Life:
Biotech solutions bringing health to living organisms and environment supported
by mass spec-focused research platform
Facts
FUNDING SCHEME: Coordination and support actions (Supporting)
SPECIFIC PROGRAMME: CAPACITIES (7.Framework Programme)
CALL IDENTIFIER: FP7-REGPOT-2012-2013-1
PROJECT DURATION: 36 (+6) months
BUDGET: EUR 5 214 534
EC CONTRIBUTION: EUR 4 667 006
GRANT AGREEMENT NO: 316094
Objectives
MOBI4Health project will increase the potential of the Intercollegiate Faculty of Biotechnology
University of Gdańsk and Medical University of Gdańsk (IFB) in terms of widening and modernization of its research technologies and will expand the innovative dimension of its scientific achievements through establishing the Centre of Molecular Biotechnology for Healthy Life: MOBI4Health
Centre. Almost 1.5 million EUR allowed the purchase of equipment enabling future cutting-edge
multidisciplinary research focusing on making life healthier. The implementation of the action plan is
going to strengthen IFB’s human potential and allow to join leading European scientific institutions
establishing standards in biotechnology.
Action Plan – Implementation of MOBI4Health Activities 2013 - 2016
Increasing Human Potential
Conferences and Workshops
Experienced scientists and experienced specialists for
the new IFB mass spec core facility will be employed in
order to improve the level of knowledge and skills of
the staff at IFB and significantly increase the research.
IFB will organise two international conferences and
four combined hands-on practical workshops/seminars based on the newly established Mass-Spec
Core Facility in order to promote an international
exchange of knowledge.
Twinning & Networking
Twinning and networking activities will increase the
scientific expertise and human potential of IFB and
contribute to its’ integration with the scientific community. Different kinds of visits by IFB scientists at the
partnering institutions and foreign researchers at IFB
as well as participation of MOBI4Health staff in international and regional key events have been planned.
Innovation Capacity Building
A wide scope of measures is planned to achieve the
goal of increasing the position of IFB among Polish
and international research institutions with regard to
its innovation capacity through building a strong and
stimulating research-business environment and attracting industrial and business partners in the region,
country and abroad.
Equipment – Improvement of Research Capacity
Two mass spectrometers and additional equipment will give a substantial input for the increase of
research potential.
28
Improvement of Visibility
Promotional activities and dissemination of knowledge aims at increasing visibility at the European and
regional level with focus on all potential stakeholders.
Management
The objective is to ensure a smooth and effective
implementation of the project. Activities comprise
coordination of all project activities, in particular the
financial and administrative management as well as
monitoring of risk on the one hand and success indicators on the other.
External Evaluation
An independent assessment of the MOBI4Health
Centre’s research potential performed by experts
appointed by the European Commission will evaluate
the level of achievement of project objectives and
perspectives on sustainability of project output.
Cooperation with European Partners
International cooperation within MOBI4Health includes joint activities with the following European
partner organisations:
University of Nottingham
United Kingdom
www.nottingham.ac.uk
Laboratory Agronomy &
Environment ENSAIA-INPL
France
www.ensaia.inpl-nancy.fr
Philipps-Universitaet Marburg
Germany
www.uni-marburg.de
INSA Lyon
France
www.insa-lyon.fr
University of Konstanz
Germany
www.uni-konstanz.de
Centro de Investigaciones Biologicas
Spain
www.cib.csic.es
Federico II University of Naples
Italy
www.unina.it
Georg-August-University Goettingen
Germany
www.uni-goettingen.de
INSERM U846 Stem-cell and
Brain Research Institute
France
www.inserm.fr
Biomedical Research
Institute FORTH
Greece
www.bri.forth.gr
29
MOBI4Health Project Progress in 2015
Summary
In 2015 activities in the frame of the MOBI4Health project supported the further development
of excellence in research and innovation at IFB. Eight post-doctoral researchers, employed within
MOBI4Health, have continued their scientific work in the research teams and the recently established
Mass Spectrometry Laboratory.
Scientific cooperation with the MOBI4Health research partners have been strengthened by intensive
twinning activities in form of research stays of IFB scientists at partner institutions (8 stays) and
visits of partners at IFB (14 visits). The International Steering Committee met in July 2015 for an
annual meeting in order to provide recommendations for further activities.
Results of IFB research have been presented at numerous conferences and scientific workshops,
including 9 events in Poland, 15 events in Europe and 6 events outside Europe. The project
supported three open access publications in Q1 class scientific journals in 2015. Scientific workshops,
lecture sessions, practical courses and a large international conference contributed to an intensified
dissemination and broadening of knowledge on current research trends.
IFB cooperation offer has been presented at networking and brokerage events in order to raise IFB’s
visibility and establish new collaboration. In the region, IFB has actively participated in the process
of formulating Regional Smart Specialisation Strategies of the Pomorskie Region and has entered
the partnership: Long Healthy Life – Medical Technologies for Civilization Diseases and Healthy Aging.
Numerous activities have contributed to disseminating information on molecular biotechnology among non-researchers in order to raise interest for science and biotechnology-related issues.
These actions included among others, lecture sessions for school classes, cooperation with the local
radio station Radio Gdańsk and online presence in social networks.
Research Conferences, Workshops, Trainings
MOBI4Health 3rd Mass Spectrometry Workshop: Innovations in environmental friendly
productions of lipids and proteins for industry, 17 - 19 March 2015
The 3-days workshop consisted of a lecture session and two days of practical courses. Practical
courses were conducted on the systems SCIEX QTRAP™ 6500 and TripleTOF® 5600 + available on the
IFB Mass Spectrometry Laboratory.
Lectures and practical training sessions at the workshop were delivered by experienced researchers
and experts from the field:
▪ Quentin Enjalbert, Sciex, Germany
▪ Prof. Ivo Feussner, University of Goettingen, Germany
▪ Dr Andreas Marquardt, University of Konstanz, Germany
▪ Cyrus Papan, Sciex, Germany
▪ Dr Michal Sharon, Weizmann Institute of Science, Israel
▪ Dr Piotr Stefanowicz, University of Wrocław, Poland
▪ Prof. Roman Zubarev, Karolinska Institute, Sweden
In total, 60 researchers participated in the workshop
(39 in practical courses).
MOBI4Health 4th Mass Spectrometry Workshop: Innovations in discovery of potential new
pharmaceuticals, 7 - 9 July 2015
This 3-days workshop consisted of a practical course on genomics with the use of the MassARRAY®
system (Agena Bioscience), a lecture session covering the genomics and proteomics approach and a
practical course on proteomics with the use of the systems QTRAP™ 6500, MALDI TOF/TOF™ 5800
and TripleTOF® 5600+ (Sciex).
Lectures and practical training sessions at the workshop were delivered by experienced researchers
and experts from the field:
▪ Dr Kathrin Breuker, Institute of Organic Chemistry, University of Innsbruck, Austria
30
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
Jason Causon, Sciex, UK
Sebastian Fabritz, Sciex, Germnay
Prof. Agata Kot-Wasik, Gdańsk University of Technology, Poland
Dr Jenny Renaut, Luxembourg Institute of Science and Technology, Luxemburg
Céline Leclercq, Luxembourg Institute of Science and Technology, Luxemburg
Dr Timo Wagner, Agena Bioscience, Germany
Dr Anna Woziwodzka, IFB UG & MUG, Poland
Dr Agnieszka Woźniak, KU Leuven, Belgium
Dr Agnieszka Bernat-Wójtowska, IFB UG & MUG, Poland
Prof. Mikhail Zarayskiy, Pavlov First Saint Petersburg State Medical University, Russia
In total, 59 researchers participated in the workshop (48 in practical courses).
Joint 7th Conference of the Polish Society for Experimental Plant Biology
and the Intercollegiate Faculty of Biotechnology UG & MUG, 8 - 11 September 2015
The 4-days conference was divided into six thematic sessions:
▪ Natural Variation and Phenomics
▪ System and Synthetic Biology
▪ Plant Development and Gene Regulation
▪ Plant-Microbe Interactions
▪ Plant Responses to Abiotic Stress
▪ Social and Commercial Aspects of Contemporary Biotechnology
In total, the conference gathered 242 participants. Lectures were held by 25 invited speakers from
Germany, UK, USA, Italy, the Netherlands, Belgium and by 23 researchers whose presentations have
been selected from the received abstracts. In addition, conference participants had the possibility of
presenting their research during two poster sessions, where in total 144 posters have been presented.
The event was held under the honorary patronage of the National Centre for Research and
Development, the Ministry of Science and Higher Education, the Rector of the University of Gdańsk
and the Rector of the Medical University of Gdańsk.
Ministry of Science
and Higher Education
Republic of Poland
31
Lecture Session: Possibilities of Mass Spectrometry, 26 June 2015
Five lectures have been dedicated to disseminate knowledge about mass spectrometry and it’s
applications as well as possibilities of the recently established Mass Spectrometry Laboratory at IFB
to young researchers from the University of Gdańsk and other entities. 52 participants attended
these presentations.
Euphresco III: Dickeya & Pectobacterium Meeting, 22 - 24 November 2015
Euphresco is a network of organisations funding research projects and coordinating national research in
the phytosanitary area. Scientists from Europe, Israel and South Africa met at IFB to discuss topics such
as Plant-pathogen interaction, Epidemiology and Control, Diagnostics, Monitoring of Pectynolytic Bacteria. The meeting gathered 44 participants working in plant biotechnology and 24 presentations
were held.
Science Dissemination
Lectures for School Classes
In order to strengthen cooperation with local schools and raise interest in biotechnology research among young people, IFB organized several lectures for school classes in April - May 2015.
The events attracted approx. 270 participants from 10 schools in the region.
Topics presented by IFB Professors to pupils covered:
▪ Computer simulations – modeling of microworld
(Prof. Rajmund Kaźmierkiewicz)
▪ Dark and light sides of espresso – short history of
coffee and its importance for people (Prof. Jacek Piosik)
▪ The world under the microscope – microbes
around us (Prof. Sylwia Jafra)
▪ Bacteria for man: possibilities of utilisation spores
in biotechnology (Prof. Michał Obuchowski)
▪ Biotechnology and the origin of man
(Prof. Jarosław Marszałek)
▪ DNA synthesis factory (Prof. Igor Konieczny)
▪ Known, little-known and unknown chemical molecules on guard of the natural environment purity
(Prof. Andrzej C. Składanowski)
Debate on GMO plants
An active discussion event with the participation of IFB researchers, students and school pupils.
Open Access publications supported from the MOBI4Health project in 2015:
▪ Martyna Krejmer, Iwona Skrzecz, Bartosz Wasag, Boguslaw Szewczyk and Lukasz Rabalski. The genome of Dasychira
pudibunda nucleopolyhedrovirus (DapuNPV) reveals novel genetic connection between baculoviruses infecting
moths of the Lymantriidae family. BMC Genomics 2015, 16(1): 759 (1-13) (doi: 10.1186/s12864-015-1963-9).
▪ Wawrzycka Aleksandra, Gross Marta, Wasążnik Anna, Konieczny Igor. Plasmid Replication initiator interactions with
origin 13-mers and polymerase subunits contribute to strand-specific replisome assembly. Proceedings of the National
Academy of Sciences of the United States of America 2015, 112(31): E4188-E4196 (doi: 10.1073/pnas.1504926112).
▪ Czajkowski Robert, Ozymko Zofia, de Jager Victor, Siwińska Joanna, Smolarska Anna, Ossowicki Adam, Narajczyk
Magdalena, Łojkowska Ewa. Genomic, Proteomic and Morphological Characterization of Two Novel Broad Host Lytic
Bacteriophages ΦPD10.3 and ΦPD23.1 Infecting Pectinolytic Pectobacterium spp. and Dickeya spp. PLoS ONE 2015,
10(3): art. no e0119812 (1-23) (doi:10.1371/journal.pone.0119812
32
RESEARCH GROUP PROFILES
Laboratory of Biologically Active Compounds
Introduction of antibiotics to medicine has nearly entirely
eradicated multiple species of pathogenic microorganisms.
However, widespread misuse of these drugs led to the emergence of multiple drug-resistant bacterial species. Considerable
problems regarding antibiotic resistance promote the development of novel antibacterial drugs. Search for more effective ways
to treat multiple drug-resistant nosocomial infections stimulates
the investigation of natural compounds as alternative treatment.
Aleksandra Królicka, PhD
She graduated from Academy of Agriculture and Forestry in Olsztyn in 1994, received PhD in biology (1999) at University
of Gdansk and habilitation in biotechnology sciences (2011) at Wrocław University of Environmental and Life Sciences.
Group leader since 2012. Author of 57
peer-reviewed publications and 3 course
books, supervisor of 3 ongoing PhD’s.
Research group
Matylda Sidwa-Gorycka, PhD
Rafał Banasiuk, PhD student
Marta Krychowiak, PhD student
Angelika Michalak, PhD student
Research conducted by the Laboratory of Biologically Active Compounds
includes topics relating to the production of biologically active compounds in plant in vitro cultures and
focuses on the discovery and study
of natural and synthetic antibacterial
and antifungal compounds (synthetic
peptides, nanoparticles of silver and
other metals).
An estimated 50 000 biologically active compounds are derived
from plants. They are termed secondary metabolites, as they are
not involved in the basic metabolism of plants but are developed
as a result of specialised metabolic pathways. Plants have been a
source of pharmaceutical compounds since the 7th century B.C.
In the second half of the 19th century the interest in phytotherapy decreased and herbs were replaced with synthetic pharmaceuticals. Yet, in the age of chemotherapy a new threat has appeared. The number of drug side effects has increased; moreover
not all synthetic drugs are as effective as natural ones. This has
led to an increased interest in phytopharmaceuticals.
Our interests include the use of secondary metabolites derived
from in vitro and in vivo cultured plant tissues against bacterial
and fungal pathogens of humans and plants. In order to increase
the content of biologically active secondary metabolites we use
abiotic and biotic elicitors, precursors of metabolic pathways and
transformation of Agrobacterium rhizogenes. The use of biotic
and abiotic elicitors increase the synthesis of pharmacologically
active compounds (bactericidal and cytotoxic activity). Elicitors
play a significant role in the production of secondary metabolites.
They induce defense responses in plants, which leads to the
accumulation of secondary metabolites. In some cases
compounds not synthesized normally by plants in their natural
environment are produced upon elicitation.
Hairy roots obtained after transformation of plant tissue with
A. rhizogenes are considered as fast growing cultures rich in
secondary metabolites. The ability to transform plants is
conferred by the possession of a Ri (root inducing) plasmid.
T-DNA fragment of this plasmid containing tms and rol genes
is transferred and integrated into the plant genome. These genes seem to have a number of functions, one of which is to
increase the level of biologically active auxins in transformed tissue.
Cultures of genetically transformed tissue (hairy roots or
teratomas) are an efficient source of species and tissue specific
secondary metabolites.
In order to increase the antimicrobial and antifungal effect of the
plant extracts, they are tested in combination with other active agents (synthetic peptides, nanoparticles of silver and other
metals). Nowadays the number of chemotherapy treatments based on the multidrug concept continuously increases. The basis
of effective multidrug chemotherapy is the multi-target action
34
of several drugs leading to the same therapeutic effect while significantly lowering the production cost. Synergistic combinations
of drugs may be extremely effective against antibiotic resistant
microorganisms. The mechanism of action of plant extracts, nanoparticles and synthetic peptides on bactera is another important part of our current research.
Ongoing research aims at elucidating the mechanisms determining antimicrobial and antifungal activity as well as developing
and improving the process of nanoparticle production.
Recent publications
▪ Banasiuk R, Frackowiak JE, Krychowiak
▪
▪
M, Matuszewska M, Kawiak A, Ziabka
M, Lendzion- Bielun Z, Narajczyk M,
Krolicka A. 2016. Synthesis of antimicrobial silver nanoparticles through a
photomediated reaction in an aqueous
environment. Int. J. Nanomedicine, 11:
315 - 324.
Krychowiak M, Grinholc M, Banasiuk R,
Krauze-Baranowska M, Glod D, Kawiak
A, Krolicka A. 2014. Combination of
silver nanoparticles and Drosera binata extract as a possible alternative for
antibiotic treatment of burn wound
infections caused by resistant Staphylococcus aureus. PLOS ONE 9(12):
e115727.
Szpitter A, Narajczyk M, Maciag-Dorszynska M, Wegrzyn G, Lojkowska E,
Krolicka A. 2014. Effect of Dionaea
muscipula extract and plumbagin on
maceration of potato tissue by Pectobacterium atrosepticum. Ann. Appl.
Biology 164: 404 – 414.
Patents
▪ Patent application nr P.405473: The
purification process of chlorophyll
containing extract of plant secondary
metabolites. Banasiuk R., Michalak A.,
Krychowiak M., Królicka A., 30.09.2013
Scientific collaboration
▪ Biomax S.A.; Gdyńskie Centrum
Innowacji
▪ Université de Lorraine France
▪
▪
▪
▪
Laboratoire Agronomie et
Environnement Nancy-Colmar,
(prof. Frederic Bourgaud)
Medical University of Gdansk,
Department of Pharmacognosy, Poland
(prof. Mirosława Krauze-Baranowska
and prof. Maria Łuczkiewicz)
Medical University of Lodz, Department
of Biology and Pharmaceutical Botany,
Poland (prof. Halina Wysokińska)
AGH-University of Science and Technology, Poland (Magdalena Ziabka, PhD)
West Pomeranian University of
Technology, Poland
(Zofia Lendzion-Bielun, PhD).
35
Laboratory of Biological Plant Protection
Our research focus on the understanding of the mechanisms
occurring during the plant-bacteria interaction. We are also
interested in bacteria-bacteria and bacteria fungus interaction including plant pathogens and beneficial bacteria with
emphasis on Pseudomonas spp.
Sylwia Jafra, PhD
She received her PhD in biological sciences (1999) at the University of Gdansk. She
carried out several lab trainings in INSA
de Lyon, France (1996-1998). She accomplished her postdoctoral training at Plant
Research International, Wageningen, The
Netherlands (2001-2003). She got habilitation in biochemistry (2011). She is a Vice
Dean for students’ and educational affairs
(2012-2016) and a member of Marie Curie
Fellows Association.
Research group
Dorota Krzyżanowska, PhD;
Magdalena Rajewska, PhD
Adam Ossowicki, PhD student
Magdalena Jabłońska, PhD student
PhD Thesis
▪ Dorota Krzyżanowska „The in vitro and
in planta antagonism of Pseudomonas
sp. strain P482 against bacterial phytopathogens of the genera Pectobacterium and Dickeya”, (2015)
36
To survive in a competitive environment, the plant-associated Pseudomonas produce a set of biologically active compounds, many of them with antimicrobial activity. However,
the knowledge concerning the antibacterial activity of beneficial Pseudomonas spp., is limited. The tomato rhizosphere
isolate Pseudomonas donghuensis P482 inhibits the growth
of pathogenic bacteria and fungi. In the last decade, the
new strains of invasive soft rot bacteria from Pectobacterium
(P. carotovorum subsp. brasiliense and P. wasabie) and Dickeya
(D. solani) genera have been isolated from the symptomatic
potato plants. The threat of spread of these pathogens calls
for development of an effective and environmental friendly
control strategy. Considering the on-going reinforcement
of the integrated plant protection policy in Europe (Directive 2009/128/ec of the European Parliament and of the
Council), the new strategies require alternative plant protection tools to chemical agents, such as natural compounds
and microorganisms.
In our current projects we verify the potential of the
P. donghuensis P482 strain to antagonize bacterial plant
pathogens (selected strains of Dickeya and Pectobacterium
genera) and to analyze the genetic background of P482
antimicrobial activity by genome data mining approach
combined with Tn5 mutagenesis.
Genome data mining in determination of genes
involved in the antimicrobial activity of Pseudomonas
donghuensis against plant pathogenic bacteria.
Sequencing of P482 genome was a basis for the bioinformatics analysis, for which the tools such as antiSMASH and
BAGEL3 were employed. Genome mining of P482 does not
reveal the presence of the genes responsible for the synthesis
of known antimicrobial factors. However, the ClusterFinder
algorithm, designed to detect atypical or novel classes of
secondary metabolite gene clusters, predicted 18 such clusters in the genome of the P482. In parallel approach, the
Tn5 mutagenesis of P482 strain was performed, which resulted in selection of the mutant affected in antimicrobial
activity. The Tn5 insertion was located in the gene encoding HcpH/HpaI aldolase, and present in one of the “hypothetical” clusters predicted by ClasterFInder, together with
the downstream homologues of four nfs genes, previously
reported to account for the production of a nonfluorescent siderophore by P. donghuensis HYST (1). We verified
the importance of the genes, consisting of the HcpH/HpaI
cluster, for antibacterial activity towards soft rot pathogens.
Three genes downstream nfs cluster and nfs cluster itself
are essential for antibacterial activity of P482 towards selected strains of Pectobacterium and Dickeya genera.
The potential of P. donghuensis P482 to protect plant tissue
against soft rot bacteria depends on the pathogens and
a type of plant tissue.
Recent publications
Plant tissue protection assay performed on potato tubers and leaves of chicory heads by co-inoculation of the
mixtures of the pathogen and P482 strains revealed that
P482 was able to protect potato tubers against maceration activity of tested strains of Pectobacterium sp., but not
against Dickeya sp. However, this strain occurred very powerful against Dickeya sp. on chicory head leaves. These
results indicate on the plant tissue-specific effectiveness of
P482 against Dickeya strains. Moreover, the mutant of P482
unable to inhibit the growth of Dickeya sp. in vitro remained
capable of protecting chicory head leaves towards Dickeya
sp. Therefore, we might suppose that different mechanisms
govern the antagonism of P482 against Dickeya sp. in the
in vitro and in planta conditions.
The minitubers of potato and seeds of tomato and
maize were coated with the gfp variant of the tested strain
suspended in 1% carboxymethylcellulose and potted
into soil. The plants were grown in a growth chamber.
The roots and stems of tomato were collected after 3 weeks of
plant growth and enrichment strategy. The obtained results
showed, that P482 effectively colonised roots of tomato,
maize and potato (Fig.1 left panel) and it can only establish stable population on tomato stems (Fig.1 right panel).
All these suggest that P. donguensis is an interesting organism for studding the plant-bacterium and plant-pathogen
and beneficial bacterium interaction.
▪
▪ Song C., Schmidt R., de Jager V.,
▪
Krzyzanowska D., Jongedijk E.,
Cankar K. Beekwilder J., van Veen A.,
de Boer W., van Veen J.A and Garbeva,
P. (2015). Exploring the genomic traits of fungus-feeding bacterial genus
Collimonas. BMC Genomics, 16: 1103.
Czajkowski R., Pérombelon M.C.M.,
Jafra S., Lojkowska E., Potrykus M.,
van der Wolf J.M. and Sledz W. (2015).
Detection, identification, and differentiation of Pectobacterium and Dickeya
species causing potato blackleg and
tuber soft rot: a review. Annals of Applied Biology, 166: 18-38.
Krzyzanowska D.M, Ossowicki A.,
Jafra S. (2014). Genome sequence
of Pseudomonas sp. P482, a tomato
rhizosphere isolate with a broad-spectrum antimicrobial activity. Genome
Announcements, 2(3): e00394-14.
▪ University of Nottingham, Centre for
▪
▪
▪
▪
Biomolecular Science, Nottingham, UK
(prof. Paul Williams)
Nederlands Instituut voor Ecologie
(NIOO-KNAW), Wageningen,
The Netherlands (Paolina Garbeva, PhD)
Wagenignen UR, Plant Research
International, Wageningen, The
Netherlands (Jan van der Wolf, PhD)
ARO, The Volcani Center, Institute of
Plant Sciences, Ornamental Plants
and Agricultural Biotechnology Dep.,
Bet-Dagan, Israel (Iris Yedidia, PhD)
Research Institute of Horticulture,
Skierniewice, Poland
(Joanna Puławska, PhD)
Figure 1.Colonization of the potato root (left) and tomato stem by GFPtagged Pseudomonas donghuensis P482. The image was obtained
with Leica TCS LSI Macro Confocal. Green pseudocolor indicates the
position of GFP-expressing mini-colonies (Krzyzanowska et al., 2012).
Scale bar 500 μm.
Future plans
Future plans include further exploration of the mechanism(s)
responsible for the plant tissue protection against Dickeya sp.
by P. donguensis P482 and the isolation and identification of
the compound(s) responsible for bacterial growth inhibition.
37
Laboratory of Biomolecular Systems Simulations
Rajmund Kaźmierkiewicz, PhD
He obtained his master degree in chemistry in 1992 at the Chemistry Department of Gdańsk University, where he
was employed until 2007. He defended
his PhD thesis in 1997. After postdoctoral
fellowship (1997-1998) at the Department
of Chemistry, University of Arizona, Tucson, USA he visited several times (overall
3 years) the Department of Chemistry and
Chemical Biology, Cornell University, USA.
Since 2007 is a team leader of Biomolecular Systems Simulations Research Group.
Research group
Dominika Jankowska, PhD
Kamil Krystian Belau, PhD student
Mateusz Pikora, PhD student
Tomasz Makarewicz, PhD student
Marcin Augustyniak, PhD student
Inga Jamrożek, PhD student
PhD Theses
▪ Paweł Gruszczyński „The use of mo-
▪
▪
lecular modeling methods in conformational analysis and the investigations of protein-ligand interactions
using the serine-threonine PrkC kinase
complexes with ATP and complexes of
sodium ion channels with μ-conopeptides as the examples”, (2010)
Roch Jędrzejewski „Theoretical modeling
of the tertiary structures and complexes of proteins from the Ankyrin,
MarR and GNAT families, using the molecular dynamics simulations and the
functional analysis” (2011)
Dominika Jankowska „The application
of computational methods in research
on the bacterial proteins TraR and
AiiO”, (2016)
38
The tools used in our research activities are all contemporary molecular modeling techniques including, but not limited
to, quantum ab-initio methods, semi-empirical methods,
empirical – molecular mechanics (classical force fields
methods), molecular dynamics simulations, Monte-Carlo
methods, calculations taking into consideration the free
energy changes and the influence of solvent. The computers used in research include five supercomputers placed
near the beginning of top500 list including the second fastest computer in EU which is IBM Blue Gene located in
Forschungszentrum Juelich, Germany.
Each of our computer modeling projects takes into consideration the complete environment with the presence of all
molecules, as they appear in the living organisms. We are
engaged in a couple of state-of-the-art research activities,
these are:
Development of the new method of the reconstruction of
full-atom protein structure from the coarse-grained protein
structure representation or just Cα-trace. The method consists of the Monte Carlo search of global minimum of orientation of the peptide group dipoles. The function minimized
is the total energy of interaction of dipoles.
Simulations of folding pathways of quadruplex structures of
DNA molecules. We investigate all possible pathways of a
series of the DNA quadruplex structures reported so-far in
the PDB database. The DNA quadruplex structures are simple models of human telomere DNA fragments. We obtain
the quadruplex structure formation pathways and stability
of non-B DNA.
Molecular docking studies including virtual screening.
The method treats molecular complexes as a pair of objects.
The ligand molecule is flexible and its conformation is
accommodated to the binding site of the receptor using
genetic algorithm minimization in the simplified force field.
Figure 1. Two representations of the structure of methylenetetrahydrofolate reductase/genistein complex in the presence of FAD.
Molecular protein-protein docking studies. This project is
in accord with current trends as “blind” protein-protein
docking studies are the subject of another series of experiments termed the “communitywide experiment on the
comparative evaluation of protein-protein docking for structure prediction“, in short - CAPRI. This project involves molecular dynamics simulation of the catalytic domain of the
serine – threonine PrkC kinase and its complexes with ATP
derivatives. The PrkC is able to trans autophosphorylate the
second molecule of this enzyme, therefore we investigate
also the possible structures of the PrkC dimers.
Recent publications
The homology modeling study of the structure of an
Ankyrin-F-box protein from Orf virus. We use an extensive
sequence analysis, fold recognition and homology modeling
which resulted so-far in final structure which after quality
assessment was used in energy minimization and molecular
dynamics simulations.
▪
Computer simulations of possible ligand escape pathways.
There are quite a few known protein-ligand complexes. The
still unsolved problem is how they are formed. Currently it
is possible only to simulate realistic physics-based process
of dissociating ligand from the complex or simulations of
so-called “escape pathways”. For that purpose we use the
computer modeling technique called Random Acceleration
Molecular Dynamics.
The molecular modeling of the TraR protein and autoinducer molecules involved in quorum sensing mechanism.
Dominika has modeled TraR/DNA complexes with
N-acyl-L homoserine lactones: OOHL, OHL, HHL, OHHL and
inhibitors: patulin, droseron, plumbagin and 3-chloroplumbagin for the first time, using Autodock and molecular dynamics in the AMBER empirical force field.
The QM/MM studies on the possible mechanism of action
of AiiO enzyme interacting with the N-acyl-L homoserine
lactones. There are contradicting literature reports regarding the substrates degradation pathways. They can be
verified using the QM/MM simulations.
▪ Michał Grabowski, Bogdan Banecki,
Leszek Kadziński, Joanna Jakóbkiewicz
-Banecka, Rajmund Kaźmierkiewicz,
Magdalena Gabig-Cimińska,
Grzegorz Węgrzyn, Alicja Węgrzyn,
Zyta Banecka-Majkutewicz, “Genistein
inhibits activities of methylenetetrahydrofolate reductase and lactate
dehydrogenase, enzymes which use
NADH as a substrate”, Biochemical and
Biophysical Research Communications,
(2015) Sep 25;465(3):363-7.
Yu.I. Prylutskyy, V.V. Cherepanov, M.P.
Evstigneev, O.A. Kyzyma, V.I. Petrenko,
V.I. Styopkin, L.A. Bulavin, N.A.
Davidenko, D. Wyrzykowski, A. Woziwodzka, J. Piosik, R. Kaźmierkiewicz,
U. Ritter, “Structural self-organization of С60 and cisplatin in physiological solution”, Physical Chemistry Chemical Physics, (2015),
Oct 21;17(39):26084-92.
▪ Prof. Harold A. Scheraga from the
▪
▪
▪
▪
Department of Chemistry and Chemical Biology, Cornell University, USA.
Prof. Baldomero M. Olivera from the
Department of Biology, University
of Utah
Prof. Grzegorz Bulaj from the Department of Medicinal Chemistry University of Utah, USA
Prof. Ulrich H. E. Hansmann from
the John von Neumann Institute for
Computing, Germany.
The past collaboration with prof. Victor Hruby from Department of Chemistry and Biochemistry University of
Arizona, Tucson, USA.
Future plans
Prof. Kaźmierkiewicz’s team plans to predict the molecular
docking pathways in the homoserine/TraR complex using
Random Acceleration Molecular Dynamics method. Another
subject of future research is to implement molecular dynamics algorithm in torsional space into the ECEPP empirical
force field. One of subjects involves computer simulations
of self-assembly process of protein capsids of viruses.
It is possible currently with the exception that one needs to
design coarse-grained protein models and evaluate protein-protein motions using the simplified empirical force field.
39
Jacek Piosik, PhD
He graduated (1994), received PhD (1999)
and habilitation (2011) at University of
Gdansk in biological sciences. In 2012 he
was appointed associate professor at the
University of Gdansk.
Research group
Anna Woziwodzka, PhD
Agnieszka Borowik, PhD student
Grzegorz Gołuński, PhD student
Monika Romanik, PhD student
PhD Thesis
▪ Anna Woziwodzka „Stacking interactions: the role of caffeine and other
methylxanthines in modulation of
activity of heterocyclic aromatic amines” (2014)
40
Laboratory of Biophysics conducts research on biologically
active low molecular weight compounds, such as anticancer drugs, environmental mutagens and carcinogens, toxins,
and substances with chemopreventive properties. The main
objectives of our research are to describe the mechanisms
of action of a wide variety of toxic substances, to search for
protective compounds and to reveal their mechanisms of
action, to develop new effective methods to modulate the
activity of drugs with particular emphasis on drugs used in
anticancer therapy.
Our recent studies focused on examination of possible direct
interactions of small biologically active compounds with
commonly used antitumor drugs. The best example of such
studies is research on interactions between pentoxifylline
and doxorubicin – the drug often used in anticancer therapy.
Pentoxifylline as a modulator of anticancer drug
doxorubicin: reduction of doxorubicin DNA binding and
alleviation of its biological effects
Doxorubicin (DOX) – anthracycline antibiotic – is widely used
for treatment of numerous cancer types, such as bladder,
prostate or breast cancers, and many others. DOX has numerous systemic adverse effects including cardiomyopathy,
hematologic disorders, bone marrow suppression as well
as toxic effects at injection sites, such as tissue necrosis or
veins inflammation. Numerous reports indicate possibility
of DOX activity modulation as well as side-effects reduction
by drug administration with other biologically active compound capable to form transient, non-covalent complexes with
the drug. Pentoxifylline (PTX) - member of methylxanthines,
synthetic derivative of caffeine - is a prospective candidate
for such modulation. In our recent work we showed that
PTX can directly interact with DOX in the presence of DNA
forming stacking complexes. It should be noted that DOX
can strongly intercalate to DNA, and additionally it is able
to self-aggregate, mainly to form dimers. Using UV-vis spectroscopy we analyzed mixtures containing DOX, PTX and calf
thymus DNA. We were able to observe four main forms of
DOX molecules in the mixture: DOX alone, DOX in a dimer,
DOX in stacking complexes with PTX, and finally DOX intercalated into DNA. We developed new mathematical model
to analyze such complex mixtures. Based on this model, we
were able to establish all components’ concentrations as
well as all association constants which describe DOX-PTX,
DOX-DOX and DOX-DNA complexes formation. What is
more, we observed that DOX-PTX stacking complexes formation disrupts equilibrium between all DOX’ forms, and in
consequence causes to de-intercalation of DOX molecules
from DNA (Fig.1).
Recent publications
▪ Gołuński G., Borowik A., Derewoń-
Fig.1. Pentoxifylline promotes de-intercalatation of doxorubicin from DNA
To check possible influence of PTX on the DOX mutagenic
activity we used Salmonella typhimurium TA98 strain in the
Ames test. We showed that mutagenic activity of DOX – PTX
mixtures is lowered when PTX concentration increases in the
mixture, and it is strongly associated with presence of DOX in
a free uncomplexed form, which was determined using new
mathematical model. What is more, using the MTT cytotoxicity assay we showed that PTX has protective effect against
the DOX biological activity towards non-cancerous HaCaT
eukaryotic cells, but we did not observe such protection on
cancerous MCF-7 and MEL-Juso cell lines. Confocal microscopy
observations of the HaCaT cell line revealed decrease in the
DOX fluorescence when the anticancer drug was administered
together with PTX (Fig.2).
▪
▪
ko N., Kawiak A., Rychłowski M.,
Woziwodzka A., Piosik J. Pentoxifylline as a modulator of anticancer
drug doxorubicin. Part II: assessment
of pentoxifylline influence on biological activity of the drug. Biochimie
2016, 123: 95–102 (doi: 10.1016/j.
biochi.2016.02.003).
Gołuński G., Borowik A., Wyrzykowski D., Woziwodzka A., Piosik J.
Pentoxifylline as a modulator of anticancer drug doxorubicin. Part I: reduction of doxorubicin DNA binding.
Chemico-Biological Interactions 2015,
242:
291-298
(doi:
10.1016/j.
cbi.2015.10.008).
Prylutskyy Yu. I., Cherepanov V. V.,
Evstigneev M. P., Kuzyma O. A.,
Petrenko V. I., Styopkin V. I., Bulavin L.
A., Davidenko N. A., Wyrzykowski D.,
Woziwodzka A., Piosik J., Kaźmierkiewicz R., Ritter U. Structural self-organization of C60 and cisplatin in physiological solution. Physical Chemistry
Chemical Physics 2015, 17(39): 2608426092 (doi: 10.1039/c5cp02688a).
▪ Faculty of Physics, National Techni▪
Fig.2. Pentoxifylline changes doxorubicin fluorescence localization pattern
in the living cells.
These results suggest that non-covalent stacking interactions
between DOX and PTX may affect biological activity of the
drug. We intend to investigate such interactions and their
biological effects basing on other drugs, cell lines and animal
models in the future.
▪
▪
▪
cal University of Sevastopol, Crimea
(Prof. Maxim P. Evstigneev)
Department of Biophysics, Taras
Shevchenko National University of
Kyiv, Ukraine (Prof. Yuriy Prylutskyy)
Faculty of Chemistry, Gdańsk University of Technology (Prof. Jan Mazerski)
Faculty of Pharmacy, Medical University of Gdańsk (Prof. Mirosława
Krauze-Baranowska)
Faculty of Chemistry, University
of Gdańsk (Dariusz Wyrzykowski, PhD)
Carbon nanoparticles, especially fullerenes, are another
group of biologically active compounds studied by our group in international collaboration. We recently showed that
fullerene C60 non-covalently interacts with doxorubicin and
cisplatin. However, the mechanism of such interaction still
remains unknown, but we and others showed that such interactions affect biological activity of these anticancer drugs.
Explanation of this phenomenon is also one of our targets for
future investigations. Finally, we intend to examine substances
with chemopreventive properties in the close future. Plant
polyphenols, e.g. cyanidins from raspberries, are a primary
targets of our investigations. These studies will be performed
in close collaboration with Faculty of Pharmacy (MUG) and Laboratory of Biologically Active Compounds from our faculty.
41
Laboratory of Biopolimer Structure
Stanisław Ołdziej, PhD
Received his PhD in Chemistry at the
University of Gdańsk (1995). He carried
out his postdoctoral training at the University of Montreal, Canada (1996-1998)
working with prof. F. Major on modeling
structure of small RNA molecules. In the
years 2001-2004 he carried out his second postdoctoral training at the Cornell
University, USA working with prof H.A.
Scheraga on predicting three-dimensional structure of proteins. He became a habilitation doctor at 2005. Author of more
than 110 per-reviewed publications.
Research group
Wioletta Żmudzińska, PhD,
Maciej Baranowski, PhD student,
Aleksandra Lewandowska, PhD student
Anna Fel, PhD student
Marcel Thiel, PhD student
PhD Theses
▪ Agnieszka Lewandowska „Mecha-
▪
▪
nism of formation of the C-terminal
β-hairpin of the B3 domain of the
immunoglobulin binding protein G from
Streptococcus”, (2009)
Wioletta Żmudzińska „Turn forming
sequences and their impact on early
stages of protein folding”, (2012)
Anna Hałabis „The temperature influence on the three-dimensional structure of proteins. Study on model system
mini-protein tryptophan cage and its
variants”, (2015)
Our research is mostly focused on understanding principles governing the protein folding process. Majority of known protein
sequences are able to form well organized three-dimensional
structures spontaneously. Structural self-organization of proteins is called protein folding, and despite biological importance this process is not well understood yet. Investigation of folding process is very complicated taking into account its speed
(most of globular proteins fold in fractions of milliseconds) or
sensitivity of the process to environment conditions (temperature, ionic strength, pH, metal ions). One of the approaches to
tackle the protein folding problem is to develop a theoretical
model capable of reproduction of known experimental data as
well as prediction of properties not available so far. Our group
in cooperation with groups of professor H.A. Scheraga (USA)
and professor A. Liwo (Poland) participates in development
of what is called a coarse-grained (simplified) model of polypeptide chain called UNRES (UNited RESidues), see Fig. 1. The
UNRES (www.unres.pl) program is used to investigate protein
folding mechanism, to simulate protein dynamics over long
period of time or to predict three-dimensional structure based
on protein amino acid sequence alone. In recent years UNRES
model has been extended to be able to treat also nucleic acids
(DNA or RNA) as well as complexes formed between proteins
and nucleic acids. Currently, our work in UNRES project is focused on two specific aims: temperature influence on structure
of proteins and identification of folding initiation sites. Folding/
unfolding of a protein induced by temperature is a well-known
phenomenon; however detailed mechanism of such process is
not well understood. Complete or partial unfolding of proteins
and aggregation associated with them bring more and more
attention nowadays, especially in the context of cell malfunction or death. Using NMR spectroscopy and molecular dynamics simulations we could provide detailed (at atomic level resolution) mechanism of how native functional structure of the
protein responds to temperature change (see Fig. 1)
Fig. 1. The UNRES united-residue model of polypeptide chains. The interaction sites are side-chain ellipsoids of different sizes (SC). The polar interaction sites bearing point dipoles (depicted as red arrows) are colored blue and
the virtual bonds are shown as thick black lines.
42
So far we studied several small proteins (up to 60 residues) and we have concluded that: i) every studied protein
responded to temperature change in its specific way; ii)
increasing temperature leads to increased dynamics of residues which form hydrophobic core of the protein; iii)
complete unfolding of a protein is associated with breaking
of only one specific interaction between hydrophobic amino
acid side chains.
Recent publications
▪ Wiśniewska
▪
▪
Fig.2. The ensembles of conformations build based on restraints derived
from the NMR spectra of the HP35 protein registered at 278, 293 and 313 K.
During our study of temperature influence on protein structure, we found that some parts of protein sequences possess
the ability to keep an organized structure (similar to those
observed for native folded state) regardless of temperature
at which measurements are performed. So far, we identified several motifs of the lengths 6-10 amino acid residues
which form turn-like structures in temperatures range from
278 K up to 320 K. Moreover, conformational properties of
such motifs are preserved when they are studied as peptides without the context of the whole protein. The three
dimensional structure of such peptides is much more
dynamic than regular proteins; nevertheless some conformational properties are clearly visible. We believe that motifs
with so pronounced conformational properties seeded over
protein sequences are so called “nucleation sites” of the protein folding process. Identification of such nucleation sites
has great importance from practical point of view and allows
a more rational design of protein sequences which will form
well defined three-dimensional structures less prone to
unfolding or aggregation. Moreover, because peptides
identified as possible nucleation sites can form fairly well
defined three-dimensional structures, some of them
possess catalytical properties (hydrolase) which we would
like to study in the future.
Marta,
Sobolewski
Emil, Ołdziej Stanisław, Liwo Adam,
Scheraga Harold A., Makowski Mariusz.
Theoretical studies of interactions between O-phosphorylated and standard amino-acid side-chain models in
water. Journal of Physical Chemistry B
2015, 119(27): 8526-8534
Yu Hyun Young, Ziegelhoffer Thomas, Osipiuk Jerzy, Ciesielski Szymon
J., Baranowski Maciej, Zhou Min,
Joachimiak Andrzej, Craig Elizabeth A.
Roles of Intramolecular and Intermolecular Interactions in Functional Regulation of the Hsp70 J-protein Co-Chaperone Sis1. Journal of Molecular Biology
2015, 427(7): 1632-1643
Zaborowski Bartłomiej, Jagieła Dawid,
Czaplewski Cezary, Hałabis Anna, Lewandowska Agnieszka, Żmudzińska Wioletta, Ołdziej Stanisław,
Karczyńska Agnieszka, Omieczynski
Christian, Wirecki Tomasz, Liwo Adam.
A Maximum-Likelihood Approach to
Force-Field Calibration. Journal of
Chemical Information and Modeling
2015, 55(9): 2050-2070
▪ Prof. H.A. Scheraga, Cornell University
USA
▪ prof A. Liwo, University of Gdańsk,
Poland
▪ prof J. Brasuń, Medical University of
Wrocław, Poland
▪ prof. E. Łodyga-Chruścińska, Technical
University of Lódź, Poland
▪ prof. K. Łukaszuk, Invicta Clinic/Medical University of Gdańsk
43
Our research is focused on cancer cell biology, with special
emphasis on invasion and metastasis. We are interested in
mutual interactions of cancer cells with their microenvironment, and their implications for prognosis and therapy of
cancer patients. Experiments are carried in vitro, in vivo in
animal models and in the clinical setting using broad spectrum of methods. There are three main lines of research
related to: I) interaction of cancer cells with endothelium,
II) the role of complement system in tumor evasion and III)
evaluation of novel biomarkers of cancer progression.
Prof. Jacek Bigda
Received his PhD in Medicine at the
Medical University of Gdansk (1990).
He carried out postdoctoral training at
the Weizmann Institute of Science (19911993), working with Prof. David Wallach.
He underwent also shorter trainings in
the Central Laboratory of Dutch Red Cross
(1991) and Medical University of Hannover, Germany (1995, 1996). He became a
habilitated doctor at 1996. In 2001 he was
appointed associate professor at the Medical University of Gdansk and was awarded the full professorship at 2005.
Research group
Prof. Jacek Bigda, MD, PhD
Anna J. Żaczek, PhD
Marcin Okrój, PhD
Patrycja Koszałka, PhD
Anna Supernat, PhD
Grzegorz Stasiłojć, PhD
Dominika Czaplińska, PhD student
Monika Gołuńska, PhD student
Martyna Filipska, PhD student
Anna Nagel, PhD student
PhD Theses
▪ Aleksandra Markiewicz „Analysis of
▪
invasion and metastasis-related markers in breast cancer patients„ (2015)
Anna Supernat „Clinical significance of selected molecular markers in
endometrial cancer” (2015)
Vascular endothelium, is presently looked upon as an
important autocrine/paracrine/endocrine organ that regulates number of cardiovascular functions. Healthy endothelium
is essential for undisturbed functioning of the cardiovascular system, while endothelial dysfunction characterized by
impaired production of vasoprotective endothelial mechanisms and excessive production of pro–oxidant, pro–thrombotic, pro–inflammatory endothelial mechanisms leads to
various pathologies. Endothelial dysfunction contributes
to invasion, survival, chemoresistance and metastasis of
cancer cells by various mechanisms. Treatment of cancer
metastasis still represent „unmet medical need”. Migrating
cancerous cells cannot survive for a long time in the circulation and unrestrained trafficking of these cells to endothelium seems critical in metastasis. We have demonstrated that
CD73/ecto-5’-nucleotidase knockout slows down the vascularization of subcutaneous tumors and decreases the number of
experimental lung metastases.
The complement system as a part of innate immune
system is aimed to recognition and elimination of invading
pathogens. Noteworthy, complement can be also targeted
onto tumor cells. However, tumor cells evade complement
attack by overexpression of membrane-bound complement inhibitors and natural antitumor antibodies are often
present at low titers or possess low affinity. Importantly,
therapeutic modulation of complement activity emerges
as an attractive target in clinical approaches and there are
several anti-cancer drugs approved, which utilize the complement system as their effector mechanism. Laboratory of
Cell Biology undertakes projects related to the role of complement in tumor growth and anticancer therapies. Objectives include investigation of the dual role of complement in
progression of lung and breast cancer, introduction of novel
markers of complement activation for monitoring of monoclonal antibody-based immunotherapy as well as original
concept on how to turn factors fueling autoimmune events
into supporters of immunotherapy.
Our research relates also to deeper understanding of
cancer spread and metastasis formation, with special
44
interest in early dissemination of cancer cells and significance of epithelial-to-mesenchymal transition in breast cancer. Through the comprehensive investigation of primary
tumors, lymph node metastases and circulating tumor cells
(CTCs) in blood of patients we are looking into the metastasis cascade to gain deeper knowledge about new molecular markers that could improve diagnosis and treatment of
breast cancer. Our team is experienced in carrying out projects related to development and validation of biomarkers
as well as designing diagnostic methods for their reliable
investigation in routine approach. Currently various projects focused on development of novel blood-based qPCR
assays to monitor response to the therapy more precisely
are underway. They concern molecular profiling of CTCs
in breast cancer, ctDNA in ovarian cancer and miRNA from
tumor-derived exosomes in colon cancer. Additionally,
biomarkers and molecular pathways associated with response to tamoxifen in breast cancer are investigated.
Recent publications
▪ Koszałka P, Gołuńska M, Stanisławow-
▪
▪
ski M, Urban A, Stasiłojć G, Majewski
M, Wierzbicki P, Składanowski AC,
Bigda J. CD73 on B16F10 melanoma
cells in CD73-deficient mice promotes
tumor growth, angiogenesis, neovascularization, macrophage infiltration
and metastasis. Int J Biochem Cell Biol
2015; 69: 1-10.
Okroj M, Holmquist E, Nilsson E, Anagnostaki L, Jirström K, Blom AM. Local expression of complement factor I
in breast cancer cells correlates with
poor survival and recurrence. Cancer
Immunology Immunother 2015; 64:
467-78PK
Markiewicz A, Książkiewicz M, Wełnicka-Jaśkiewicz M, Seroczyńska B,
Skokowski J, Szade J, Żaczek AJ. Mesenchymal phenotype of CTC-enriched
blood fraction and lymph node metastasis formation potential. PLoS One
2014; 9:e93901.
Patents
▪ PCT/EP2015/070526 Marcin Okroj,
Anna M Blom „Antibodies specific for
complement component C4d and uses
thereof”
▪ Institute of Immunology and Cell BioFig. 1. Liquid biopsy – blood-based assay for detection of tumor cells
circulating in the blood of cancer patients
The research of the team is situated at the edge of molecular biology and clinical oncology with mission to translate
the results obtained in the laboratory into clinical practice
and thus contribute to more effective and individualized
management of cancer patients.
logy, University of Stuttgart, Germany
and
Vessels
Institute
in Dusseldorf, Germany
Cytomics Laboratory of Prince Philip
in Valencia, Spain
Institute of Tumor Biology of the Eppendorf University Hospital, Hamburg,
Germany
Department of Translational Medicine,
Lund University, Malmö, Sweden
Department of Hematology, Karolinska
Institute, Stockholm, Sweden
Functional Genomics of Ovarian Cancer Laboratory, University of Cambridge, Cancer Research UK Cambridge Institute, United Kingdom
▪ Heart
▪
▪
▪
▪
▪
45
Laboratory of Evolutionary Biochemistry
Proteins are complex and dynamic macromolecules. In
all living cells molecular chaperones play critical roles in
remodeling protein structure i.e. assisting protein folding and
preventing protein aggregation, facilitating assembly and disassembling of protein complexes and modulating protein:
protein interactions.
Our goals are to understand the basis of: (1) the mechanism of
action of molecular chaperones in specific complex biological
processes and (2) the evolutionary mechanisms behind functional divergence amongst molecular chaperones allowing
them to assist in specific cellular processes.
Prof. Jarosław Marszałek
He graduated from the University of
Gdansk (1982), received his PhD in biochemistry at the Medical University of
Gdansk (1988) and received his habilitation in biological sciences at the University of Gdansk (1997). He carried out
postdoctoral work at the Department of
Biochemistry, Michigan State University,
USA (1989-1991) and Institut fur Physiologische Chemie der Universitat Muenchen (1995). He has been a Professor in
biological sciences since 2004. Beginning
in 1999, he has been a Visiting Associate
Professor at the Department of Biochemistry, University of Wisconsin-Madison,
where he collaborates with professor Elizabeth A. Craig.
Research group
Rafał Dutkiewicz, PhD, Hab.
Bartłomiej Tomiczek, PhD,
Mateusz Manicki, PhD student
Julia Majewska, PhD student
Michał Rogaczewski, PhD student
Wojciech Delewski, PhD student
Małgorzata Nowak, PhD student
PhD Theses
▪ Grzegorz Ciesielski „Role of Molecular
▪
▪
Chaperone Hsp40 (Mdj1) in Maintenance of Mitochondrial DNA” (2011)
Szymon Ciesielski „Characterization
of Interaction Between J-type Protein Jac1 and Isu1 Protein Participating
in Biogenesis of Iron-Sulfur Clusters”
(2012)
Jacek Kominek „Molecular Evolution of Eukaryotic Hsp70 and Hsp40
Chaperones”
46
In particular, we are interested in the role of the Hsp70 chaperones and their J-protein co-chaperones in the important
mitochondrial processes such as (1) maintenance and propagation of mitochondrial DNA (mtDNA) and (2) biogenesis of
enzymes containing iron-sulfur cluster (FeS) prosthetic groups. Both processes are essential for cell survival and are also
implicated in mitochondria related diseases in humans. As a
model system, we study yeast (Saccharomyces cerevisiae and
other related species), which allows us to combine genetic
analysis with molecular biology and biochemical approaches.
MtDNA is assembled into nucleoprotein comp-lexes termed nucleoids, which
are the functional
unit of mtDNA propagation, segrega tion and expression.
A diverse group of proteins has been found to be associated with
nucleoids. We recently discovered that all detectable Mdj1,
the most abundant mitochondrial matrix J-protein and Ssc3,
a low abundant Hsp70, are nucleoid associated. We aim to understand the molecular function(s) of Hsp70 chaperone system
in the nucleoid complex. Specifically, we ask whether its function is restricted to mtDNA maintenance and propagation or
whether the nucleoid serves as a center for protein folding in
the mitochondrial matrix.
Mitochondria contain a complex system for assembly of iron-sulfur cluster (FeS) prosthetic groups and their
insertion into proteins. A specialized
Hsp70/J-protein molecular chaperone pair is a critical part of this system,
interacting specifically with the scaffold protein on which FeS clusters are first built and facilitating
cluster transfer to recipient protein. We aim to unravel the
molecular mechanisms of this dedicated chaperone system.
Recent developments in phylo-genomics prompted us to expand our
research into the field of protein
evolution. We have discovered that
the three members of the Hsp70
family present in S. cerevisiae mitochondria arose by gene duplication and are unique to S. cerevisiae and closely related species.
This allows us to ask what molecular mechanisms have governed formation and divergence of duplicated mtHsp70s.
Such questions are of general interest as gene duplication
is considered a major source of new proteins. Our goal
is to determine what structural and functional changes
have occurred during Hsp70s evolution that governed their post-duplication divergence. We also ask how multiplication of Hsp70s affected their interactions with J-protein
co-chaperone partners and client proteins.
Recent publications
▪ Kominek J, Marszalek J, Neuvéglise
▪
▪
▪
C, Craig EA, and Williams BL (2013)
The Complex Evolutionary Dynamics
of Hsp70s: A Genomic and Functional
Perspective Genome Biology and Evolution 5: 2460-2477
Manicki M, Majewska J, Ciesielski
S, Schilke B, Blenska A, Kominek J,
Marszalek J, Craig EA, Dutkiewicz R
(2014) Overlapping Binding Sites of the
Frataxin Homologue Assembly Factor
and the Heat Shock Protein 70 Transfer Factor on the Isu Iron-Sulfur Cluster
Scaffold Protein J. Biological Chemistry
289: 30268-30278
Wojciech Delewski, Bogumila Paterkiewicz, Mateusz Manicki, Brenda
Schilke, Bartlomiej Tomiczek, Szymon
J. Ciesielski, Lukasz Nierzwicki, Jacek
Czub, Rafal Dutkiewicz, Elizabeth A.
Craig, Jaroslaw Marszalek (2015) Iron–
Sulfur Cluster Biogenesis Chaperones:
Evidence for Emergence of Mutational
Robustness of a Highly Specific Protein–Protein Interaction. Mol. Biol. and
Evol. in press
Szymon J. Ciesielski, Brenda Schilke,
Jaroslaw Marszalek, Elizabeth A. Craig (2016) Protection of scaffold protein
Isu from degradation by the Lon protease Pim1 as a component of Fe-S cluster biogenesis regulation. Mol. Biol.
Cell in press
▪ Prof. Elizabeth A. Craig Department of
▪
Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA
Prof. Roland Lill Institut für Zytobiologie, Philipps-Universität Marburg,
Robert-Koch-Str. 6, 35032 Marburg,
Germany
47
Our research includes two main fields of interest: basic research related to process of formation and germination of
the Bacillus subtilis spore and applied focused on use of the
spore as universal carrier of peptides or proteins for variety
application.
He graduated from University of Gdansk
in 1993, received PhD in biology (1997) at
University of Gdańsk and habilitation in
biological sciences (2006) and was awarded the full professorship at 2014. Since
2004 he has been working at Medical
University of Gdańsk. He carried out postdoctoral work at University of Paris XI,
France. Author of more than 50 peer-reviewed publications. He is Vice-Dean for
Science at IFB.
Research group
Krzysztof Hinc, PhD
Adam Iwanicki , PhD
Alessandro Negri, PhD student
Wojciech Potocki, PhD student
Anna Grela, PhD student
Tomasz Łęga, PhD student
Marta Hubisz, PhD student
Basic research is focused on different aspects of sporulation
process during which site specific gene expression lead to
functional diversification of ancestor cells after asymmetrical
division. In course of such a process, the cell which will be
converted in metabolically dormant spore undergo as several changes including transition DNA from B for to A as well
as gaining several protective layer surrounded developing
spore. Coordination of such process, and mechanism of deposition of coat proteins is investigated in our laboratory.
We focused on the role of PrpE phosphatase in such process.
This enzyme is involved in the controlling thickness of inner
spore coat. From the other hand, also we pay attention to the
germination process, when dormant spore is converted into
vegetative cells. In this path we investigate mechanism of action GerA receptors, which trigger germination in response to
presence L-alanine or L-valine in the environment. As part of
this pathway we are trying to build the model of GerA receptor using bioinformatics approach supported by biochemical
experiments.
As part of investigation of sporulation process and spores we
pay attention to influence of stress response on such process as well as dinucleotide tetraphosphates present in the
living cells.
We also investigate in the swarming which allow bacteria to
colonize the agar plates. This process is one of social behaviour of B. subtilis, because close cooperation of‚ swarmer-cells’
is necessary for this type of movement (Fig. 1).
PhD Theses
▪ Małgorzata Stasiłojć „Vaccine against
▪
Helicobacter pylori based on Bacillus
subtilis spores” (2015)
Krzysztofa Nagórska „Genetic basis of
exopolysaccaride production during
biofilm formation by Bacillus subtilis”
(2008)
Figure 1. Swarming pattern produced by different derivatives
of B. subtilis 168 on B media.
48
Applied research conducted in our laboratory also concern the spore but from different angle. The spore as form
of the cells which should survive different harsh condition
is extremely resistant for temperature, changes in humidity, low pH, UV irradiation as well as proteolytic enzymes.
All this properties make spore a very good choice as carrier
particle. This is also supported by the fact, that the external shield of the spore consist of proteins. These create an
opportunity to place peptide or protein of choice on the
surface of spores by simple creation fusion genes between
parts coding coat proteins and coding for passenger part.
Using this approach we create a set of spores presenting
antigens of two pathogenic bacteria: Helicobacter pylori
and Clostridium difficile. Such recombinant spores are used
for oral or intranasal immunisation of laboratory animals
in order to protect them from infection of pathogens. To
make this work more efficient a set of vector for creation
of recombinant spores was developed. For maximizing the
chance of creation of efficient spore based vaccine we
also investigate the mechanism of interaction between
administrated spores and immune system components.
As additional project we also have shown that spores may
serve as good support for enzymes which displayed an
enhanced stability in comparison with soluble form.
Recent publications
▪ Stadsiłojć M., Hinc K., Peszyńska-Sularz
▪
▪
G., Obuchowski M., Iwanicki A., 2015,
Recombinant Bacillus subtilis spores
elicit Th1/Th17-polarized immune response in a murine model of Helicobacter pylori vaccination. Molecular
Biotechnology 57: 685-691.
Iwanicki A., Piątek I., Stasiłojć M., Grela A., Łęga T., Obuchowski M., Hinc K.,
2014, A system of vectors for Bacillus
subtilis spore surface display. Microbial
Cell Factories 13:30
Hinc K., Stasiłojć M., Piątek I.,
Peszyńska-Sularz G., Isticato R., Ricca E.,
Obuchowski M., Iwanicki A., 2014,
Mucosal adjuvant activity of IL-2 presenting spores of Bacillus subtilis in a
murine model of Helicobacter pylori
vaccination. PLoS ONE 9:e95187
Patents
▪ „Oral vaccine containing spores of
▪
▪
Bacillus subtilis and its application for
immunisation against Helicobacter
pylori” granted at 2014-06-17, number:
398658
„New probes for detection bacteria of
the species Acinetobacter baumannii,
oligonucleotides and the protocol for
analysis of medical and environmental samples” granted at 2015-12-01,
number: 401061
Oral vaccine against Clostridium difficile infections based on Bacillus
subtilis spores as carriers, selected spore coat genes and FliD antigen. Granted
at 11.02.2016. Number 402193.
▪ Laboratory of microbiology, University
▪
▪
Figure 2. Bacillus subtilis spore image taken by Atomic Force Microscope
of Frideric II (Naples, Italy), professor
Ezio Ricca
Military Institute of Medicine (Warsaw,
Polska), Zbigniew Dąbrowiecki, PhD
Department of Immunology and
Infection Biology, University of Lodz,
prof. Magdalena Chmiela
49
Received his PhD in Molecular Biology at
the University of Gdansk in 1994, habilitation in 2000 and professor title in 2004.
He carried out postdoctoral training at
UCSD, USA. He is a member (secretary
2010-2012), of International Society of
Plasmid Biology and COST Biomedical
Domain (2008-2015). He was awarded
by EMBO and HHMI YIP Programmes. He
got prestigious awards from Foundation
for Polish Science and Polish Ministry of
Science. He is a Dean of IFB UG & MUG.
Our research is focused on the analysis of molecular mechanisms responsible for DNA replication and stable maintenance of extra-chromosomal genetic elements in bacteria.
We use as a model RK2 plasmid that belongs to the group
of broad-host-range replicons that can be stably maintained
and transferred between cells of various bacterial species,
including plant, animal and human pathogens. The research
utilizing such a unique system, allowing for the analysis of
cellular mechanisms in various organisms, makes the significant contribution towards the general understanding of
the fundamental cellular processes important for future
development of new antimicrobial therapeutic strategies.
Current understanding of structural requirements for functions of multi-protein complexes formed on DNA is still limited. Especially challenging is the analysis of intrinsically disordered proteins and their complexes with single-stranded
DNA (ssDNA). In our investigations we focus on (i) multi-molecule complexes formed on DNA by replication initiation
proteins (Rep), their structural bases, functions and dynamics, (ii) investigations of the mechanism of protease activity on substrates bound to DNA, and (iii) analysis of the function of plasmid encoded post segregational killing systems
in the context of its components’ interactions with DNA and
their stability.
Research group
Katarzyna Bury, PhD
Urszula Uciechowska, PhD
Katarzyna Węgrzyn, PhD
Andrzej Dubiel, PhD student
Marta Gross, PhD student
Anna Karłowicz, PhD student
Małgorzata Ropelewska, PhD student
Aleksandra Wawrzycka, PhD student
Elżbieta Zabrocka, PhD student
PhD Theses
▪ Magdalena Rajewska „13-mer motifs
▪
▪
of replication origin of plasmid RK2 as
a structural elements important for helicase activation” , (2013) (Award from
Polish Prime Minister)
Sławomir Kubik „Activation and proteolysis of plasmid RK2 replication
initiation protein in E. coli cells” , (2011)
Marcin Pierechod „Degradation of
plasmid initiation protein TrfA by E. coli
protease ClpXP” , (2008)
Fig. 1 Model of proteolysis in plasmid DNA processing. The model indicates proteolysis as a factor important for plasmids stable maintenance in
bacterial cells. In our studies we investigate how DNA influance protease
activity and how formation of specific nucleoprotein complexes affects
their stability and therfore plasmid maintainance.
By performing in vivo and in vitro experiments including reconstituted DNA replication assays, real time kinetics of protein-DNA complexes, Mass Spectrometry (MS) and Atomic
Force Microscopy (AFM) we uncovered new concept of the
formation of Rep complexes at plasmid replication origins.
We described structure of Rep protein, containing three Wing
Helixes (WH), bound with double-stranded DNA (dsDNA) and
discovered, that similar as chromosomal DnaA, it also interacts
50
with ssDNA within replication origin (Wegrzyn K. et al., Nucleic
Acids Res. 2014). This interaction is specific to one DNA strand
only, requires sequence motifs and is essential for plasmid
DNA replication.
Our recent study on the replisome assembly at plasmid RK2
replication origin (Wawrzycka A, et al., Proc Natl Acad Sci U
S A. 2015) revealed that specific interaction between the
plasmid Rep protein and β subunit of DNA Polymerase III
holoenzyme (β-clamp) is required for polymerase complex
assembly at plasmid origin. We showed that QLSLF motif within
replication initiator as well as clamp loader complex, DnaA,
helicase and primase are crucial for loading the β-clamp at
plasmid DNA. With the use of in vitro replication assays reconstituted with 18 purified replication proteins we conclude
that strand specific interaction of Rep protein determines DNA
strand for replisome assembly at the plasmid origin and thus
the direction of DNA replication. Currently conducted experiments are directed towards understanding of the regulatory
mechanisms involving β-clamp interaction with host and plasmid encoded proteins.
We extended our investigations on the role of proteases in
nucleoprotein complex metabolism (Kubik S., et al., Nucleic
Acid Research 2012). E. coli Lon protease mutants defective
in interaction with DNA were obtained and their phenotypes
were described. Structural bases for the protease interaction
with DNA has been identified. We conduct studies to describe
how cytosolic proteases process proteins within nucleoprotein
complexes and how their proteolytic activity affects plasmid
methabolism.
Recent publications
▪ Wawrzycka A, Gross M, Wasaznik A,
▪
▪
Konieczny I. Plasmid replication initiator interactions with origin 13-mers
and polymerase subunits contribute
to strand-specific replisome assembly.
Proc Natl Acad Sci U S A. 2015; 112(31):
E4188-96.
Wegrzyn K, Fuentes-Perez ME, Bury
K, Rajewska M, Moreno-Herrero F,
Konieczny I Sequence-specific interactions of Rep proteins with ssDNA
in the AT-rich region of the plasmid
replication origin Nucleic Acids Res.
2014;42(12):7807
Konieczny I, Bury K, Wawrzycka A,
Wegrzyn K. Iteron Plasmids Microbiol
Spectr. 2014;2(6).
▪ CIB-CSIC (Madrid, Spain) Prof. Rafa▪
▪
▪
el Giraldo, Prof. Ramon Diaz-Oreja,
Prof. Gloria del Solar Dongil
University of Idaho (USA) Prof. Eva Top
CNB-CSIC (Madrid, Spain)
Prof. Fernando Moreno-Herrero,
Prof. Jose Maria Valpuesta
IIMCB (Warsaw, Poland)
Prof. Janusz Bujnicki
Fig. 1. Model of the plasmid RK2 replication initiation protein TrfA in the
complex with double stranded DNA fragment of the plasmid replication
origin. Three DNA binding domains (DBD) each containing Wing Helixes
(WH) responsible for the protein interaction with DNA have been identified.
The model has been obtained and verified with using homology modeling, molecular dynamics (MD), genetic screening, mutant phenotypic in vivo analysis
and biochemical analysis of constructed mutants. Mass Spectrometry (MS)
of crosslinked nucleoprotein complexes were used for identification of protein
residues interacting the specific nucleotides of the plasmid replication origin.
51
Laboratory of Molecular Diagnostics
Our research includes two main fields of interest: research related to the photodynamic inactivation (PDI) of bacterial infections as well as the application of modern tools of molecular
biology and diagnostics (with focus on mass spectrometry, MS)
in the study of stem cells, metabolic and infectious diseases.
Prof. Krzysztof P. Bielawski
He graduated from University of Gdansk
in 1985, received PhD in medical biology (1999) at Medical University of Gdansk
and habilitation in biological sciences
(2006). He carried out postdoctoral work
at University of Muenster, Germany, Lund
University, Sweden and INSERM U827,
France. He is a full-professor in biological
sciences since 2011. Author of more than
90 peer-reviewed publications, supervisor
of 8 finished and 4 ongoing PhD’s. He is a
Director of the Technology Transfer Office
at UG and CEO of TechTransBalt Ltd., the
UG company for commercialization.
Research group
Agnieszka Bernat-Wójtowska, PhD; Mariusz Grinholc, PhD; Joanna Nakonieczna
PhD, Tomasz Romanowski, PhD; Magda
Rybicka, PhD; Alicja Sznarkowska, PhD,
Anna Woziwodzka, PhD; Anna Wróblewska, PhD;
PhD students:
Monika Kossakowska-Zwierucho,
Grze- gorz Fila, Katarzyna Meller,
Aleksandra Rapacka-Zdończyk
PhD Theses
▪ Alicja
▪
▪
▪
Sznarkowska „Activation of
TAp73 protein as a strategy to kill
cancer cells deprived of p53 tumor supressor”, (2015)
Magda Rybicka „Mechanism of TAp73
activation by a plant-derived proteasome inhibitor in cancer cells”, (2015)
Anna
Kostecka „The influence of
hepatitis B virus (HBV) polymorphism
on the response to antiviral therapy in
chronically infected patients”, (2015)
52
Photodynamic inactivation of bacteria as an alternative
to antibiotics.
According to the latest report by the European Medicines
Agency (EMEA) and the European Centre for Disease Control
and Prevention (ECDC), the emerging and growing multidrug
resistance of microorganisms poses a huge threat to the health and lives of patients both in Europe and around the world.
The problem of bacterial infections continue to grow,
especially in the case of multi-drug resistant strains.
In our team we are studying the mechanisms, which govern
different response of microorganisms to photoinactivation,
including biofilm formation, antioxidative enzymes activity,
DNA damage, bacterial transporters. As the one of the main
limitations of the method is low selectivity of PS used in PDI,
the idea is to design a PS molecule efficient against Gram(+)
and/or Gram(-) pathogens, specifically multiresistant strains
and functionalisation of the PS molecule with a cell delivery
systems to improve the action of PDI. PS must be accumulated
inside the bacterial cell or in a proximity of its envelope to efficiently kill bacteria but to be non toxic for human tissue.
Current projects are designed to determine the role of photo-induced damage of genetic material and cell envelopes in
the process of antimicrobial photoinactivation and determine
the impact of photodynamic treatment on bacterial virulence factors. Preliminary studies conducted by us demonstrated
that the treatment of microorganisms with visible light significantly sensitizes them to chemotherapeutic agents against
which they showed a high resistance. This makes it possible to
restore a treatment with antibiotics that have been excluded
because of widespread of multidrug resistant microorganisms.
We strongly believe that sequential treatment of microbial
cells with visible light and then routinely used chemotherapeutic agents, can significantly reduce levels of drug-resistance and facilitate their eradication from the site of infection.
Mass spectrometry (MS) in evaluating genetic diversity and
stability of pluripotent stem cells population.
The value of nowadays cell therapy, based on induced pluripotent stem cells (iPSCs), depends on their genomic integrity.
The appearance of genomic instability and mutations during
culture of human induced pluripotent stem cells is one of the
most important obstacles tempering the hope of their safe
use in cell therapy. Aberrations, aneuploidy and changes in the
structure and number of chromosomes that occur during the
propagation of these of cells in vitro, suggest the emergence
of a significant selection pressure, leading to selection of these
cells, which in the process of adaptation acquired proliferative
advantage. In our research we aim at:
▪ understanding how changing spectrum of genetic diversity
in population of PSCs will reflect the accumulation of
chromosomal abnormalities. This aim is to be achieved by
development of indirect strategy for monitoring of genetic
drift in a population of genetically labeled cells using MS,
▪ development of rapid tests based on MS, for detection
of most prominent and common aneuploidies found in
cultures of PSCs.
Recent publications
▪ Grinholc M, Nakonieczna J, Fila G,
MS in study of genes and molecular pathways underlying
iron overload in CHC and NAFLD patients.
Chronic hepatitis C (CHC) and non-alcoholic fatty liver disease
(NAFLD) are the leading causes of chronic liver pathology in
modern world. Dysregulation of iron metabolism, commonly
diagnosed in chronic infection with hepatitis C virus (HCV) and
NAFLD, is a serious risk factor for disease progression to cirrhosis and hepatocellular carcinoma (HCC). However, genetic
factors determining development of iron overload as well
as molecular events leading to excessive iron accumulation
remain largely understudied. Therefore, our research aims
to identify genes and molecular pathways underlying iron
overload in CHC and NAFLD patients and to verify if common
mechanisms drive the excessive iron accumulation in both
diseases. Recently, we have found, that in CHC individuals single nucleotide polymorphisms within IFNL3 and IFNL4 gene
region, which closely link with patients response to IFN treatment, also associate with body iron indices.
In future research we plan to further examine molecular pathways underlying dysregulation of iron metabolism in both
CHC and NAFLD patients, by using high throughput genotyping
by MS and deep sequencing of RNA from plasma, coupled with
extensive in silico data analysis.
Development of a sensitive MS assay to monitor of HBV drug
resistance and cccDNA polymorphism in clinical samples.
There are approx. 240 million chronic carriers of hepatitis B
virus infection worldwide. These people are at risk of liver
cirrhosis with associated mortality because of hepatocellular
carcinoma and other complications. Long term therapy, that is
required due to the existence of extremely stable HBV cccDNA
within the hepatocyte nuclei, can lead to the emergence and
selection of drug resistance mutations and treatment failure.
Therefore, precise determination of drug resistant variants in
patient before treatment is important for a proper choice of
the first line potent therapy. In our study, the detection method of HBV genetic material in clinical samples with low viral
load was developed, so that performing genetic analysis was
possible on wider range of clinical samples. We showed that
use of MS for viral mutants identification in clinical practice
can provide a valuable insight into the understanding of how
resistance develops and enables early decisions of antiviral
treatment in the management of chronic hepatitis B.
▪
▪
Taraszkiewicz A, Kawiak A, Szewczyk
G, Sarna T, Lilge L, Bielawski KP. Antimicrobialphotodynamic therapy with
fulleropyrrolidine: photoinactivation
mechanism of Staphylococcus aureus, in
vitro and in vivo studies. Appl Microbiol
Biotechnol. 2015 May;99(9):4031-43.
Nakonieczna J, Kossakowska-Zwierucho M, Filipiak M, Hewelt-Belka W,
Grinholc M, Bielawski KP. Photoinactivation of Staphylococcus aureus using
protoporphyrin IX: the role of haem-regulated transporter HrtA. Appl Microbiol Biotechnol. 2015 Dec 3. [Epub
ahead of print]
Rybicka M, Stalke P, Bielawski KP. Dynamics of hepatitis B virus quasispecies
heterogeneity in association with nucleos(t)ide analogue treatment determined by MALDI-TOF MS. Clin Microbiol
Infect. 2015 Mar; 21(3):288.e1-4.
Patents
▪ Taraszkiewicz A., Nakonieczna J., Grinholc M., Bielawski KP. Pharmaceutical
And Chemical Composition Containing
Imidazoacridone Derivatives As The
Photosensitizing Agent And The Use
Thereof; PL 220370 B1 , Granted Patent, Published: Oct 30, 2015
University Hospital Schleswig-Holstein,
Kiel, Germany (Prof. Burkhard Brandt;
Institute
of
Molecular
Oncology,
Ibbenbueren (Ulf Vogt, PhD); University of
Freiburg, Germany, (Prof. Michael Nassal);
INSERM U846 Stem-cell and Brain Research
Institute, France (Prof. Pierre Savatier);
Department of Medical Biophysics,
Princess Margaret Cancer Centre/
University of Toronto, Canada (Prof.
Lothar Lilge); Department of Biophysics,
Faculty of Biochemistry, Biophysics and
Biotechnology, Jagiellonian University
(prof. Tadeusz Sarna); Department of
infectious Diseases, Medical University
of Gdansk, (Piotr Stalke, PhD).
53
CD151 regulates FGFR signaling in prostate epithelial cells
– implications for prostate cancer progression.
Alicja Grudowska, Dominika Czaplińska, Andrzej C. Składanowski,
Rafał Sądej
Prof. Andrzej Składanowski
Received his PhD in Biochemistry at the
Medical University of Gdansk (1980). He
carried out postdoctoral work at the Bern
University, Switzerland (1981, 1983) and
at Wales University College of Medicine
in Cardiff, UK working with Dr. Andrew
Newby (1988-90). Later he studied enzymology of ischemic human heart at the
Erasmus University Rotterdam, and structure of enzyme binding sites at Bremen
University. He became a habilitated doctor at 1997. In 2001 he was appointed associate professor at the Medical University of Gdansk and was awarded the full
professorship at 2007. He is a member of
the editorial board of Toxicology in Vitro
and is chairing the Gdansk Section of the
Polish Biochemical Society.
Research group
Rafał Sądej, PhD,
Kamila Kitowska-Marszałkowska, PhD,
Łukasz Turczyk, PhD student
Magdalena Mieszkowska, PhD student
Kamil Mieczkowski, PhD student
Aleksandra Rodziewicz, PhD student
PhD Theses
▪ Alicja Grudowska „Tetraspanin CD151
▪
▪
in progression of prostate cancer”
(2015)
Konrad Kleszczyński „In vitro studies
on the mechanism of toxicity of perfluorinated carboxylic acids – SAR”, (2009)
Izabela Rusiecka “Influence of ionic
liquids and perfluorinated aliphatic
substances on multixenobiotic resistance of cells”, (2009)
54
Invasion and migration of cancer cells is crucial for the formation
of secondary lesions. It is triggered by activation of different signaling cascades which can be modulated by series of regulatory
molecules. One is CD151, a member of evolutionary conserved
tetraspanin family. Four trans-membrane domains are typical for
their structure and they control a number of physiological (proliferation, motility, cell adhesion etc.) and pathological phenomena (tumour progression, metastasis) (reviewed in [1]). CD151
forms complexes with other key proteins, primarily laminin-binding integrins (α6β1, α6β4, α3β1) what triggers aggressive behavior of neoplastic cells. It has been demonstrated that high level
of CD151 correlates with poor prognosis for patients with several
human epithelial malignancies including lung, breast, liver, colon,
pancreas, kidney, oesophagus cancer and glioblastoma. Clinical
studies demonstrated positive correlation between elevated
CD151 expression and high tumour grade (reviewed in [2]). Yet
no prognostic value of CD151 level was found in colorectal and
urothelial bladder cancers, indicating its down-regulation in malignant cell. In prostate cancer, the expression of CD151 was found
to be significantly higher in poorly differentiated prostate cancer (PCa) specimens compared with benign prostate hyperplasia
(BPH). Our study aimed at investigating the CD151 role in communication between epithelial cells and tumour stroma, which is
crucial step in terms of development and progression of PCa. The
analysis showed that stimulation of BPH-1 cells with conditioned
medium from cancer-associated fibroblasts significantly enhanced their growth in three-dimensional matrigel, however being
independent from CD151 status. The FGFR signaling involved
multiple pathways including MAPK (mitogen-activated protein
kinase), PI3K/AKT/mTOR, phospholipase C γ (PKCγ), JAK, STAT and
others [3]. All of them play specific roles in controlling numerous phenomena such as cell cycle, growth, survival, apoptosis and
others. Therefore, the molecular mechanism underlying enhancement of wild type cells (CD151-positive) migration by agonist
- FGF2 was analyzed. During spreading cells, integrins are being
recruited from the cell surface to ECM proteins, what ultimately
promotes FAK and Src activation followed by their association
with other proteins including p130cas, and GTPases – Rac1 and
RhoA; all of which are considered a heart of cellular adhesive
interactions. The analysis revealed that CD151-positive cells respond to FGF2 treatment with increased activation of FGFR, as
well as to focal adhesion kinase (FAK) and to Src (see Fig. 1).
Recent publications
▪ Piasecka D, Składanowski A C.,
Figure 1. Downstream changes in phosphorylation of FGFR, FAK and Src
upon activation by FGF2 of BPH-1 cells with different expression of CD151,
FGFR1 and FGFR2. Protein expression levels of p-FAK, p-FGFR, p-Src and
Src were determined after stimulation with FGF2 in cells with different
CD151, FGFR1 or FGFR2 expression at indicated time points. Proteins were
analyzed by immunoblots.
Similar pattern was observed only for cells highly expressing FGFR1, proving CD151-regulated promigratory FGFR1
-FGF2 signaling through FAK and Src kinases. Such effect is
in agreement with the other study which revealed that activation of Src kinase under FGF2 stimuli requires specifically
FGFR1 [4].
Presented study reveals for the first time that tetraspanin
CD151 through regulation of FGFR1-FGF2 interaction may
promote invasive properties of benign hyperplastic epithelial cells through FAK and Src kinases what results in elevated
proliferation/growth and migration, contributing to prostate
cancer progression. In this system, CD151 can be considered as a positive marker in the primary tumour as its expression in non-tumourigenic prostate epithelial cells correlated
with enhancement of their migratory behavior.
[1] L. Collette, T. Burzykowski, F.H. Schröder, Prostate-specific antigen
(PSA) alone is not an appropriate surrogate marker of long-term therapeutic benefit in prostate cancer trials, Eur J Cancer, 42 (2006) 1344-1350.
[2] R. Sadej, A. Grudowska, L. Turczyk, R. Kordek, H.M. Romanska, CD151
in cancer progression and metastasis: a complex scenario, Lab Invest, 94
(2014) 41-51.
[3] A.N. Brooks, E. Kilgour, P.D. Smith, Molecular pathways: fibroblast
growth factor signaling: a new therapeutic opportunity in cancer, Clin
Cancer Res, 18 (2012) 1855-1862
[4] E. Sandilands, S. Akbarzadeh, A. Vecchione, D.G. McEwan, M.C. Frame,
J.K. Heath, Src kinase modulates the activation, transport and signalling
dynamics of fibroblast growth factor receptors, EMBO Rep, 8 (2007) 11621169
▪
▪
Kordek R, Romańska H M., Sądej R.
Aspekty regulacji aktywności receptora progesteronu (PR) - znaczcenie w
progresji raka gruczołu piersiowego
[Aspects of progesterone receptor (PR)
activity regulation - impact on breast
cancer progression]. Postępy Biochemii
2015, 61(2): 198-206
Romańska HM., Potemski P, Kusińska
R, Kopczyński J, Sądej R., Kordek R.
Expression of CD151/Tspan24 and integrin alpha 3 complex in aid of prognostication of HER2-negative high-grade
ductal carcinoma in situ. International
Journal of Clinical and Experimental Pathology 2015, 8(8): 9471-9478
Czaplińska D, Turczyk Ł, Grudowska A, Mieszkowska M, Lipińska A
D, Składanowski A C, Żaczek A J,
Romańska
H
M,
Sądej
R.
Phosphorylation of RSK2 at Tyr529 by
FGFR2-p38 enhances human mammary epithelial cells migration. Biochimica
et Biophysica Acta-Molecular Cell Research 2014, 1843(11): 2461-2470
▪ Division of Cancer Studies, University
▪
▪
of Birmingham (UK) Professor Fedor
Berditchevski,
Department of Pathology, Medical
University of Łódź (Poland) Professor
Radzisław Kordek, Dr Hanna Romańska
Celon Pharma (Poland)
Future plans
Further investigations on the role of FGFR1 in promoting
growth of cancer cells and metastasis are carried on. Chemical compounds inhibiting FGFR-associated protein kinase
are being tested as the mechanism-based anticancer.
55
The Laboratory of Biochemical Physics deals with functional analysis of the structure and function of proteins.
The team studies structural changes in proteins and the
influence of such on the activity and stability of these
compounds using advanced spectroscopic, biophysical and
biochemical techniques. Employed research techniques
include stopped flow measurements, titration and scanning microcalorimetry, biochemical and genetic fluorescent
techniques. The team is interested both in basic as well as
applied research. Apart from spectroscopic studies, members of the team specialize in chromatographic analyses
using liquid (HPLC) and gas (GC-MS) chromatography.
Bogdan Banecki, PhD
PhD, 1985, University of Gdańsk, PL Postdoctoral training: ETH Zurich, University
of Utah, USA, University of Ancona, Italy
Habilitation, 2003, University of Gdańsk,
PL Group leader since 2004
Research group
Leszek Kadziński, PhD
Michał Grabowski, PhD student
Grzegorz Gawron, PhD student
Paulina Werner, PhD student
Bartłomiej Żerek, PhD student
PhD Theses
▪ Wojciech Bartosz Sawuła „Analysis of
▪
risk factors and molecular mechanisms
of pathogenesis of ischemic stroke”,
(2009)
Leszek Piotr Kadziński, „The impact of
silicone polymers on the structure and
activity of proteins”, (2013)
56
Laboratory participates in four main projects:
▪ Studies on functions of MTHFR and CBS genes during
formation of homocysteine in the context of therapeutic
and preventive aspects in patients with ischemic brain
stroke. The aim of the research, performed in collaboration
with Medical University of Gdańsk, is to describe the
mechanism of homocysteine action in the organism as one
of risk factors in the ischemic stroke. The initial research
suggests that heat shock proteins significantly modify the
activity of the MTHFR enzyme
▪ Development and studies of biocompatible and
bioregenerative materials. We analyzed the side effects
of silicone implants by determining the influence on the
stability and structure of proteins. The aim of the current
research is characterization of interactions of small molecule
polymethylsiloxanes with proteins. The conducted research
indicates significant affinity of silicones to fibrinogen and
collagen, which can be of significance in the development
of clinical side effects of using implants.
▪ Isolation and implementation of new nutraceuticals
containing natural extracts with the use of efficient,
economical and environmentally friendly methods.
The project involves the structural identification and
determination of possible modifications for increasing
the activity and bioavailability of anti-inflammatory and
antimicrobial compounds. As a result the project would
yield a group of active compounds that will be implemented
into the industrial practice. With the collaboration between
our team and the laboratory of Biovico sp. z o.o. Gdynia,
Poland, we developed new preparation of ointment based
on one of the nutraceutical being examined in the project,
which has been already released to the market.
▪ Analysis of interactions between silica-based biomaterials
and proteins. Silica based biomaterials have gained great
interest among scientists due to the possibility of their use
in medicine as scaffolds and drug carriers. Their superiority
over other biomaterials lie in the way of their synthesis
as well as their non-toxicity and biocompatibility in vivo.
Gained knowledge could benefit in better understanding
the wound healing process and bone regeneration.
Moreover, we will study the possibility of application of the
biomaterials in the controlled drug release.
Future plans
Future plans of our laboratory involves the continuation
of the project connected with ischemic stroke risk factors.
We are planning to investigate the possible role of inhibitors of nitric oxide synthases – symmetric and asymmetric dimethyloarginine. We hope to be able to correlate
its serum level with the ischemic stroke development.
Futhermore, we aim to broaden the scope of the project
about the neutraceuticals to test different plants in the context of their neutraceutical content. According to the future analysis of silica-based biomaterials, we are planning to
investigate the interactions between those with collagen, as
well as to check this protein stability and function after being attached to the silica-based material structure. Also we
would like to examine the structure of obtained biomaterial with the use of different type of microscopy techniques,
like surface electron mictroscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM).
Basing on the gained knowledge we would broaden our project to the use of different proteins to check its interactions.
Performed research of the desired proteins will involve
their interactions with the biomaterial both external as well
as the internal one in the context of its possible use as a
drug delivery system in the future.
Recent publications
▪ Grabowski Michał, Banecki Bogdan,
▪
▪
Kadziński Leszek, Jakóbkiewicz-Banecka Joanna, Kaźmierkiewicz Rajmund,
Gabig-Cimińska Magdalena, Węgrzyn
Grzegorz, Węgrzyn Alicja, Banecka-Majkutewicz Zyta. Genistein inhibits
activities of methylenetetrahydrofolate reductase and lactate dehydrogenase, enzymes which use NADH as
a substrate. Biochemical and Biophysical Research Communications 2015,
465(3): 363-367.
Kadziński
Leszek,
Prokopowicz
Magdalena,
Jakóbkiewicz-Banecka
Joanna, Gabig-Cimińska Magdalena, Łukasiak Jerzy, Banecki Bogdan.
Effect of Silicone on the Collagen
Fibrillogenesis and Stability. Journal of
Pharmaceutical Sciences 2015, 104(4):
1275-1281.
Koper Tomasz, Polit Agnieszka, Sobiecka-Szkatula Anna, Węgrzyn Katarzyna,
Scire Andrea, Figaj Donata, Kadziński
Leszek, Zarzecka Urszula, Żurawa-Janicka Dorota, Banecki Bogdan, Lesner
Adam, Tanfani Fabio, Lipińska Barbara, Skórko-Glonek Joanna. Analysis of
the Link between the Redox State and
Enzymatic Activity of the HtrA (DegP)
Protein from Escherichia coli. PLoS ONE
2015, art. no e0117413 (1-24)
Patents
▪ The extraction method of sulfonamides, secondary metabolites or semi-synthetic compounds. The patent
application (UP RP) No. 402299 dated
2012-12-28.
▪ Medical University of Gdańsk
▪ Biovico sp. z o.o. Gdynia, Poland
57
Research: Biochemical basis for improvement of plant oil
production
Prof. Antoni Banaś
Graduated from the University of Gdańsk
in 1978, where he received PhD in biology (1985). In 1994 received habilitation in
biological sciences at Warsaw University.
He carried out post-doctoral work at Swedish University of Agricultural Sciences
and at Scandinavian Biotechnology Research AB. He is a full-professor in biological sciences since 2009. He is co-author
of 84 articles (citied around 1300 times)
and around 140 conference communications. He is also co-inventor of 8 patents
granted more than 50 times as national
patents. He is a supervisor of 4 finished
and 4 ongoing PhD’s.
Research group
Katarzyna Jasieniecka-Gazarkiewicz, PhD
Kamil Demski, PhD student,
Bartosz Głąb, PhD student
Milena Lewandowska, PhD student
PhD Theses
▪ Magdalena Miklaszewska “Substrate
▪
▪
specificity of selected fatty acid reductases and wax synthases”, (2015)
Katarzyna Jasieniecka - Gazarkiewicz
“Substrate specificity and physiological functions of selected acyl-CoA:
lysophospholipid
acyltransferase”,
(2015)
Anna Grzesiuk “Effect of graminicides
on selected processes of sensitive
plants”, (2002)
58
The research interests of the laboratory mainly concern biochemistry and biotechnology of plant lipids.
During the last few years, the laboratory participated in a
worldwide integrated project “Industrial Crops producing
added value Oils for Novel chemicals – ICON” financed by
the Seventh EU Framework Program. The key goal of this endeavour was production of different kinds of wax esters in
industrial crops, such as Crambe abbysinica, Camelina sativa
or Brassica carinata. Our lab has specialised in characterization of substrate specificities of various fatty acid reductases (FAR) and wax synthases (WS) – the key enzymes of wax
esters synthesis. Additionally, the biochemistry of wax ester
mobilisation in germinating: (a) jojoba seeds (plant naturally
accumulating wax esters) and (b) seeds of transgenic industrial crops producing wax esters have been investigated.
Several of these research strands are continued now beyond
ICON project.
Beside the above mentioned research we are involved in:
▪ Biochemical characterization and determination of
substrate specificity and physiological functions of selected
acyl-CoA:lysophospholipid acyltransferases.
▪ Biochemical characterization, determination of substrate
specificity and physiological function of enzyme of
DGAT type (acyl-CoA: diacylglycerol acyltransferase) and
PDAT-type (phospholipid: diacylglycerol acyltransferase) –
key enzymes involved in triacylglycerols biosynthesis.
▪ Potential use of biotechnology to create commercially
viable plants accumulating storage lipids in leaves and
roots.
Generally speaking, the group aims at characterisation
of different enzymes connected with lipid metabolism (Fig.
1) and evaluation of their potential application in production
of different kinds of oil (demanded by chemical industry) in
transgenic industrial oil crops as well as providing the biochemical basis for genetic engineering aimed at increase of
the oil production capacity both by traditional oilseed crops,
as well as new plants producing oil in organs other than
seeds (e.g. tubers, leaves, roots).
Recent publications
Cytosol
Plastid
Glukoza
16:0-ACP
18:0-ACP
18:1-ACP
glycolysis
▪ Lager, I., Głąb, B., Eriksson, L., Chen,
FAS
FAB2
Fatty acid elongases
Dihydroxyacetone phosphate
Acyl-CoA
pool
H2C— acyl
HO—C—H
H2C—P- choline
3-phosphoglycerol
▪
LPC
GPAT
LPCAT
TAG
LPA
LPAAT
PDAT
▪
DGAT
H2C—acyl
acyl—C —H
CPT
PDCT
Phosphohydrolase PA
PA
DAG
H2C—P- choline
PC
GPAT – acyltransferase acyl-CoA:3-phosphoglycerol; LPAAT – acyltransferase acyl-CoA:lysophosphatidic acid; DGAT
– acyltransferase acylo-CoA:diacylglycerol; PDAT – acyltransferase phospholipid:diacylglycerol; CPT – cholinephosphotransferase CDP-choline:diacylglycerol; PDCT – cholinephosphotransferase phosphatidylcholine: diacylglycerol;
LPCAT – acyltransferase acyl-CoA: lysophosphatidylcholine;
FAS – fatty acid synthase; FAB2 – stearyl-ACP desaturase
G., Banaś, A., Stymne, S. 2015. Novel
reactions in acyl editing of phosphatidylcholine by lysphosphatidylcholine transa-cylase (LPCT) and acyl-CoA:
glycerophosphocholine
acyltransferase (GPCAT) activities in microsomal
preparations of plant tissues. Planta,
241: 347-358.
Zhang, D., Jasieniecka-Gazarkiewicz,
K., Wan, X, Luo, L., Zhang, Y, Banas,
A., Jiang, M., Yangmin Gong, Y. 2015.
Molecular characterization of two lysophospholipid:acyl-CoA acyltransferases belonging to the MBOAT family
in Nicotiana benthamiana. PLOS ONE,
DOI: 10.1371/journal.pone.0144653.
Jasieniecka-Gazarkiewicz, K., Demski,
K., Lager, I., Stymne, S., Banas, A. 2016.
Possible role of different yeast and
plant lysophospholipid:acyl-CoA acyltransferases (LPLAT) in acyl remodeling
of phospholipids. LIPIDS, 51:15-32
▪ Prof Banaś’s team collaborates closely
with researchers from the Department
of Plant Breeding and Biotechnology of
the Swedish University of Agricultural
Science. Moreover, Prof Banaś’ laboratory cooperates with several leading
laboratories from Europe, USA, Canada
and China.
Figure 1.The general scheme of the biosynthesis of triacylglycerols in seeds
of oilseeds plants.
Future plans
For the nearest future, the continuation of the current work
connected with plant lipid metabolism is planned.
59
Laboratory of Plant Protection and Biotechnology
Our research includes four main fields of interest:
▪ Study of the molecular mechanisms involved in pectinolytic
plant pathogenic bacteria interaction with plant tissue, as
well as plant protection against bacteria.
▪ Metabolic pathway of coumarin biosynthesis and their
role in plant resistance to abiotic and biotic stresses.
▪ Role of naphthoquinones derived from Drosera sp. plants
in apoptosis induction.
▪ Polish orchids micropropagation and reintroduction to
natural environment.
She graduated from University of Toruń in
1977, received PhD in biochemistry (1984)
and habilitation in agricultural sciences (1991). She carried out postdoctoral
work at University of Madison-Wisconsin, USA and INSA, Lyon, France. She is a
full-professor in biological sciences since
2001. Dean of the IFB UG & MUG in years
2015-2012. Author of more than 90 peer-reviewed publications, supervisor of 17
finished and 5 ongoing PhD’s. She was a
vice-President of Committee for Biotechnology PAS (2011-2015) and is President
of the Professor Waclaw Szybalski
Foundation (from 2009).
Research group
Robert Czajkowski, PhD; Anna Ihnatowicz,
PhD; Małgorzata Golanowska, PhD; Anna Kawiak, PhD; Marta Potrykus, PhD; Joanna Siwińska, PhD; Wojciech Śledź, PhD; Małgorzata
Waleron, PhD; Joanna Znaniecka, PhD; Jakub
Fikowicz-Krośko, PhD student; Natasza Kaczyńska, PhD student; Agnieszka Misztak, PhD
student; Agata Motyka, PhD student; Sabina
Żołędowska, PhD student
PhD Theses
▪
▪
▪
Małgorzata Golanowska “Characterization
of Dickeya solani strains and identification of bacterial and plant signals involved
in the induction of virulence”, Co-promotor
Dr. N. Hugouvieux-Cotte-Patat, INSA Lyon,
France, (2015).
Marta Potrykus “Characteristics of the
molecular mechanism involved in the pathogenicity of bacteria from genus Dickeya
on plants”, Co-promotor Dr. N. Hugouvieux-Cotte-Patat, INSA Lyon, France, (2015).
Joanna Siwińska “Natural variation of Arabidopsis thaliana as a tool for study of the
biosynthesis of coumarins”, Co-promotor
Dr. Anna Ihnatowicz, (2015)
60
Study of the molecular mechanisms involved in interaction
of pectinolytic plant pathogenic bacteria and plant tissue.
The goal of the current research is to elucidate the molecular basis of the virulence of the bacteria from the genus
Dickeya and Pectobacterium on potato. Our study are concentrated on the regulation of the synthesis of enzymes
degrading plant cell wall compounds, especially pectate
lyases but also other enzymes and factors important in pathogenesis e. g. cellulases, siderophores, biofilm formation.
The study should expand the knowledge on molecular
mechanisms involved inthe interaction between plant and
bacterial cells. We are also interested in the analyze of the
pangenome and panregulon of Dickeya solani and Pectobacterium wasabiae. Mentioned microbes differ significantly in
their biodiversity level. D. solani strains exhibit homogeneity
of the genomes contrarily to their diverse virulence intensity, whereas P. wasabiae strains display higher divergence
concerning both traits indicated. Presented characteristics
determine profound potential of these species as the models
for analysis of pangenomes, core and accessory genomes. We
intend to identify structural and regulatory genes connected with virulence factors. The goal of our study is to verify whether the adaptation to live and cause disease symptoms under temperate climate conditions results from the
presence of certain genetic determinants in the genomes of
D. solani and P. wasabiae.
We are interested in developing methods for detection,
identification and differentiation of plant pathogenic
pec-tinolytic bacteria based on molecular markers.
Our studies are also devoted to the control of
plant pathogenic bacteria by newly isolated and
characterized bacteriophages with wide and narrow
host specificity. Several bacteriophages infecting bacteria from the genus Dickeya and Pectobacterium are isolated from natural environment and fully characterized.
Metabolic pathway of coumarin biosynthesis and their
role in plant resistance to abiotic and biotic stress.
The aim of this study is to characterize the functions
ofselected iron (Fe) and 2-oxoglutarate (2OG) dependent
dioxygenases (2OGD) in plant responses to various environmental stresses using a model plant Arabidopsis thaliana. We
showed that the expression levels of particular genes encoding dioxygenases are significantly and specifically induced
when plants are grown under different environmental
stresses, but the biological functions of some of them are
not yet characterized. Our aim is to better understand the
genetic and molecular basis of plant responses to different
environmental factors and possibly to get insight into the
plant adaptation to changing environmental conditions.
A set of different functional genomics techniques (ionomics,
metabolite profiling, proteomic analysis of thylakoid membranes, transcriptomics) is used, as well as the biochemical
and molecular biology methods.
Role of naphthoquinones derived from Drosera sp. in the
induction of apoptosis.
Study aimed at determining the activity of plumbagin and
ramentaceone, a constituent of the plants from genus
Drosera toward breast cancer cells and characterization of
the metabolic pathway involved in naphtochinons-mediated
cell death induction. The results showed that naphtochinons
exhibited high antiproliferative activity toward breast cancer
cells, in particular HER2-overexpressing breast cancer cells.
The mode of cell death induced was through apoptosis.
The obtained results suggest further investigation of plumbagin, its derivatives and ramentaceone as a potential therapeutic agent in breast cancer therapy, in particular HER2—
overexpressing breast cancer cells.
Polish orchids micropropagation and reintroduction to
natural environment.
Study are concentrated on development of the methods for
Polish orchids micropropagation, cryopreservation and biobanking of seeds and tissues. We are especially interested
in preservation of orchids from the species: Cypripedium calceolus, Epipactis atrorubens and Liparis loeselii.
Recent publications
▪
▪
▪
▪
Patents
▪
P.397896. Potrykus M., Śledź W., Łojkowska
E. Detection and identification of bacteria
from the species Pectobacterium caroto-
vorum subsp. carotovorum, Pectobacterium atrosepticum and genus Dickeya spp.
04.01.2016
▪
▪
▪
▪
▪
Fig. 1. A set of selected Arabidopsis thaliana natural populations (accessions) originating from different geographic regions was grown under
diverse environmental scenarios (Environment 1 – 3). Significant phenotypic variation is present among tested Arabidopsis accessions.
M. Potrykus, M. Golanowska, N. Hugouvieux-Cotte-Pattat and E. Łojkowska.
2014. Regulators involved in Dickeya
solani virulence, genetic conservation and
functional variability. Molecular Plant-Microbe Interaction. 27: 700–711.
R. Czajkowski, Z. Ozymko, V. de Jager,
J. Siwińska, A. Smolarska, A. Ossowicki,
M. Narajczyk and E. Łojkowska. 2015.
Genomic, proteomic and morphological characterization of two novel broad
host lytic bacteriophages ΦPD10.3 and
ΦPD23.1 infecting pectinolytic Pectobacterium spp. and Dickeya spp. PLOS ONE |
DOI:10.1371/journal.pone.0119812.
J. Siwińska, L. Kadziński, R. Banasiuk,
A. Olry, B. Banecki, E. Łojkowska and
A. Ihnatowicz. 2015. Dissecting the genetic
architecture of scopoletin and scopolin
biosynthesis in 1 Arabidopsis thaliana.
BMC Plant Biology 14: 280-294.
A. Kawiak and E. Łojkowska
2016.
Ramentaceone, a naphthoquinone derived from Drosera sp., induces apoptosis
by suppressing PI3K/Akt signaling in breast
cancer cells. PLOS ONE | DOI:10.1371/journal.pone.0147718.
Polish-Italian Cooperation, Canaletto Program ”Pangenomic approach to the definition of the genetic basis of pathogenicity
in the two bacterial species Dickeya solani
and Pectobacterium wasabiae causative
agent of losses in potato crops in Europe”.
Poilsh-French Cooperation, Pollonium Program “Characteristics of the molecular mechanism involved in the pathogenicity of
plant pathogenic bacteria from the genus
Dickeya on potatoes”.
Euphresco
Phytosanitary
ERA-NET,
“Dickeya and Pectobacterium species in
potato and management strategies”.
Polish Norwigian Cooperation, PoTPat –
“Potato pathogen populations in changing
climatic conditions of Norway and Poland
and the mechanisms of their interaction
with host”.
Polish-French Cooperation, “Arabidopsis
thaliana as a model organism for identification of genes determining enzymes
involved in the biosynthesis of coumarins”.
61
Prof. Krzysztof Liberek
He graduated from physics at the Technical University of Gdansk (1982), received
his PhD in biology at the University of
Gdansk (1990) and received his habilitation in biological sciences at the University of Gdansk (1996). He carried out postdoctoral work at Department of Viral,
Cellular and Molecular Biology, University
of Utah, USA (1990-91) and Department
of Medical Biochemistry, University of
Geneve, Switzerland (1992-93). He is a
full-professor in biological sciences since
2002. In 2006 he was elected to EMBO.
Research group
Anna Badowiec, PhD,
Elżbieta Chruściel, PhD
Szymon Ziętkiewicz, PhD
Tomasz Chamera, PhD student
Krzysztof Gumowski, PhD student
Agnieszka Kłosowska, PhD student
Artur Piróg, PhD student
PhD Theses
▪ Szymon Żwirowski „The mechanism of
▪
▪
chaperone-dependent disaggregation
of complexes comprising small heat
shock proteins and their substrates”,
(2016)
Łukasz Nowicki „New regulatory elements of Hsp104 disaggregase from
yeast Saccharomyces cerevisiae”,
(2014)
Natalia Lipińska „New regulatory elements of Hsp104 disaggregase from
yeast Saccharomyces cerevisiae”,
(2013)
We are interested in the role and mechanisms of chaperone proteins action in different cellular processes. The chaperone protein network controls both initial protein folding and maintenance
of proteins in the cell. The linear polypeptide chains newly synthesized on ribosomes have to fold into native threedimensional
structures. Although the native structure of a protein is principally encoded in its amino acid sequence, the process of folding in
vivo very often requires the assistance of molecular chaperones.
Chaperones also play a role downstream of protein synthesis in
a quality control system and thus are required to maintain the
proper conformation of proteins in changing environmental
conditions. Many factors leading to unfolding and misfolding of
proteins result eventually in protein aggregation. High temperature was one of the first aggregation-inducing factors studied,
and remains one of the main model approaches. With massive
protein aggregation occurring in response to heat exposure, the
cell needs chaperones to control and counteract the aggregation
process. Elimination of aggregates can be achieved by two alternative pathways, solubilization of aggregates and either refolding
of liberated polypeptides or their proteolysis. In our research we
focus on the mechanisms by which Hsp70, Hsp100 and small heat
shock proteins (sHsps) liberate and refold polypeptides trapped in
the protein aggregates.
Cooperation between Hsp100 and Hsp70
in protein disaggregation.
The Hsp100 family of chaperone proteins plays a wide variety of
important cellular functions, including survival to environmental
stress, regulation of genetic competence, transposition, proteolysis, and control of protein-based genetic element (prion). These
different roles are unified by a common biochemical mechanism,
the ability of Hsp100 proteins to promote the disassembly of aggregated proteins and high order protein complexes. During disaggregation
a polypeptide is disentangled from
the aggregate, translocated through
the central channel, and enabled
to fold into the native structure.
However, Hsp100 chaperones are
not able to act on its own. Functional cooperation between Hsp100
and Hsp70 and its cochaperones
is required at several stages of this
process. In our research we are
trying to determine the molecular
mechanism of cooperation between
chaperones from Hsp70 and Hsp100
families in disaggregation and refolding of aggregated proteins.
Figure 1. Model for the mechanism of action of Hsp70 and Hsp100 chaperones in disaggregation of protein aggregates.
62
Role of sHsps in control of aggregation and disaggregation.
Small heat shock proteins are an evolutionary conserved class
of ATP-independent molecular chaperones. Members of this
family are characterized by a low molecular mass (15-43 kDa)
and the presence of the conserved α-crystallin domain. At physiological conditions sHsps form oligomeric structures. Under
heat stress conditions deoligomerization process takes place
and sHsps form complexes with misfolded proteins, preventing
them from further aggregation and keeping them in a refoldable state that facilitates subsequent solubilisation and refolding
by AT- P-dependent Hsp70 and Hsp100 chaperones. Using different biochemical approaches we are investigating the molecular
events leading to deoligomerization of sHsps and subsequent interaction between these chaperones and their substrates leading
to formation of sHsps-substrate complexes. We also analyse the
mechanism of misfolded protein refolding from such complexes.
While the initial binding of sHsps to substrates is beneficial by
preventing the formation of large aggregates and increasing
the accessible surface for Hsp70-Hsp100 action, this interaction
also hamper Hsp70-Hsp100 association and has to be broken to
allow for substrate refolding. How this Janus-faced sHsp feature is circumvented has not been addressed so far. Recently, we
have identified a novel Hsp70 activity, displacing sHsp molecules
from the surface of the complex at the very initial phase of the
reactivation process.
Recent publications
▪ Wortmann, S.B. Ziętkiewicz, S. et al.,
▪
▪
(2015) CLPB mutations cause 3-methylglutaconic aciduria, progressive brain
atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder Am. J. Hum. Genet. 96,
245-57
Stróżecka, J., Chruściel, E., Górna,
E., Szymańska, A., Ziętkiewicz, S.,
Liberek, K. (2012) Importance of the
N- and C-terminal regions of Ibpa,
the Escherichia coli small heat shock
protein, for chaperone function and
oligomerization. J. Biol. Chem. 287,
2843-2853.
Lipińska, N., Ziętkiewicz, S., Sobczak,
A, Jurczyk, A., Potocki, W., Morawiec,
E., Wawrzycka, A., Gumowski, K.,
Ślusarz, M., Rodziewicz-Motowidło, S.,
Chruściel, E.,
Liberek, K. (2013)
Disruption of Ionic Interactions
between the Nucleotide Binding
Domain 1 (NBD1) and Middle (M)
Domain in Hsp100 Disaggregase Unleashes Toxic Hyperactivity and partial independence from Hsp70. J. Biol.
Chem. 288, 2857-2869
▪ Center for Molecular Biology of the
University of Heidelberg (Germany),
Professor Bernd Bukau
Figure 2. Model of two homodimers of sHsps, IbpA chaperone proteins
from Escherichia coli, interacting through the C-terminal motif.
Our studies contribute to the understanding of the fundamental
processes of chaperones functioning. Our long term goal
is to understand the functional interactions and crosstalk between components of a chaperone network in different cellular
processes.
63
The application of different expression systems for the production of viral proteins which can be used as potential vaccines or
constituents of modern diagnostic tests is the main field of interest of the Laboratory. Apart from using a wide array of classical methods of molecular biology, the Laboratory specializes
in expression of foreign genes in insect cells using insect cell
expression system. Some of the research projects carried out in
the Laboratory are listed below:
Graduated in 1974 at the Faculty of Chemistry , Technical University of Gdansk. Obtained PhD degree at the Faculty of Chemistry,
University of Gdansk in 1984. Habilitation
was awarded in 1996 at the Faculty of Biology, Geography and Oceanology, University of Gdansk. Full professorship since 2001
Group leader at IFB since 1996.
Postdoctoral research was done at:
University of California San Francisco, USA;
University of Utah, Salt Lake City, USA;
University of London, United Kingdom.
Research group
Ewelina Król, PhD
Łukasz Rąbalski, PhD
Dawid Nidzworski, PhD
Beata Gromadzka, PhD student
Martyna Krejmer, PhD student
Karolina Uranowska, PhD student
Krzysztof Łepek, PhD student
PhD Theses
▪
▪
▪
Łukasz Rąbalski „Application of ssDNA
separation and real-time PCR for the detection and differentiation of Newcastle
virus strains”, (2014)
Dawid Nidzworski „Novel methods for
the detection of influenza virus and Newcastle disease virus”, (2014)
Ewelina Król „Classical swine virus (CSFV)
as the model for testing the activity of
novel inhibitors against hepatitis C virus
(HCV), (2012)
64
Construction of recombinant vaccines against bird flu
viruses: H5N1, H7N9, H9N2; against human pandemic and
seasonal influenza viruses; against Newcastle virus (NDV) and
against human and animal caliciviruses (norovirus and rabbit
hemorrhagic disease virus).
The research on the construction of recombinant vaccines against human and animal influenza is carried out in close collaboration with three scientific institutions which constitute Polish
Vaccine Consortium: Institute of Biochemistry and Biophysics
Polish Academy of Sciences, Institute of Biotechnology and
Antibiotics, and National Veterinary Research Institute. Polish
Vaccine Consortium succeeded in construction of a variety of
potential anti-influenza vaccines against bird flu H5N1. Two approaches: expression of hemagglutinin in bacteria Escherichia
coli and in yeast Pichia pastoris fulfilled the requirements for
large scale protection of chickens, that is excellent protection and
very low price for a dose. At present the Consortium is working
on the construction of vaccines against two other very dangerous avian strains of influenza: H7N9 and H9N2. Simultaneously
the Consortium constructs the anti-influenza vaccines for humans, both for seasonal as well as for pandemic strains. In case
of human vaccines the criterion of low price though important,
is not crucial, therefore other expression systems such as baculovirus or mammalian cells are being used for the production of
antigens. The potential vaccines are based on the viral-like particles (VLPs), that is the outer coats of viruses without its genetic
material. Newcastle disease is a devastating disease of poultry.
We intend to change the classical approach, that is using the attenuated strains for vaccination, by replacing it with a recombinant
vaccine based on live attenuated turkey herpesvirus (licensed as
a vaccine against Marek’s disease in many countries) where two
genes of Newcastle disease virus are inserted in dispensable part
of herpesvirus genome. At present, final animal studies are being
carried out on the efficacy of this vaccine. Another approach is
to use caliciviruses for the construction of vaccines. Caliciviruses
virions are built of a single self-assembling protein with excellent
antigenic properties. Empty shells of caliciviruses, apart from being vaccines against a particular calicivirus, can accommodate
foreign peptides which can act as immunogens stimulating immunological response against other pathogens. This approach is
also intensively pursued in our laboratory.
Effect of synthetic glycosylation inhibitors on viral entrance
and propagation in host cells.
Lack of effective drugs against most of viral diseases calls for an
intensive research in this field. We have concentrated our efforts
on the development of structural analogs and mimetics of tunicamycin, an effective inhibitor of N-glycosylation of glycoproteins. A large number of synthetic compounds was obtained
from Pharmaceutical Institute in Warsaw and Silesian Technical
University in Gliwice. We have tested these compounds using
a few model viruses which included hepatitis C virus, classical
swine fever virus, pseudorabies virus and influenza A virus. A few of
these compounds exhibited promising antiviral properties and are
further studied with the aim to elucidate their mechanism of
action. Some of the inhibitors interfere with the mechanism
of glycosylation, while the other inhibit viral propagation by other
molecular mechanisms.
Monitoring of baculoviruses controlling the populations
of lepidopteran pests in forests and orchards.
Apart from being and excellent system for expression of
foreign genes, baculoviruses are used as biological pesticides
which are safe for the environment and very selective with respect to a pest. In cooperation with Forest Research Institute in
Warsaw we have isolated and performed extensive sequencing
of baculoviruses attacking gypsy moth and other members of the
family Lymantridae. These studies gave us insight into virulence
factors of this family of lepidopteran pests.
Future plans
The influenza A/H1N1 responsible for the first pandemic of the twenty-first century turned out to be relatively mild when compared to
other influenza pandemics of the past. However, such a situation
may be transient and there are concerns that the virus may reassort
during mixed infections of a single host with different variants of influenza A virus. The resulting recombinant virus may have unpredictable properties when it establishes itself in the human population.
Therefore, our future goal is to develop universal vaccine against
influenza virus which may protect against many strains of the virus.
This may be achieved by efficient production of constant regions of
viral proteins, e.g. so called stalk region of influenza hemagglutinin.
The epidemiology of viral diseases, to a large extent, is a constant chase for new pathogenic viruses. One of the emerging
threats for Middle and Western Europe is the tick-borne encephalitis virus (TBEV). Due to the changing climate conditions, the
European variant of the virus is quickly translocated to completely
new ecological niches in Europe. Additionally, there is an increasing
threat of genetic recombination between European variant and
even more dangerous Siberian variant of the virus. In our research
we are committed to interfere with the spread of this virus and we
are constructing a recombinant vaccine against TBEV as well as we
are monitoring the genetic changes of the emerging viruses.
Finally, we are preparing tools for quick molecular diagnosis (and
possibly for prevention by vaccination) of viral diseases which may
appear in the nearest future. We have concentrated our efforts on
dengue, Ebola and Zika viruses which are of increasing importance
for the whole world.
Recent publications
▪
▪
▪
Krzysztof Lepek, Beata Pajak, Lukasz
Rabalski, Kinga Urbaniak, Krzysztof
Kucharczyk, I. Markowska-Daniel and
Boguslaw Szewczyk (2015) Analysis of
Co-infections with A/H1N1 Strain Variants Among Pigs in Poland by Multitemperature Single-Strand Confor-mational Polymorphism (MSSCP),”
BioMed Res. Int , Article ID 632347, doi.
org/10.1155/2015/535908
RydzakJ, Kaczmarek R, Czerwinski M,
Lukasiewicz J, Tyborowska J, Szewczyk
B, Jaskiewicz E. (2015) The baculovirus-expressed binding region of Plasmodium
falciparum EBA-140 ligand and its glycophorin C bindingspecificity. PLoS One
14;10(1):e0115437. doi: 10.1371/journal.
pone.0115437
Krejmer , M., Skrzecz, I., Wasag, B., Szewczyk, B., Rabalski, L. (2015). The genome
of Dasychira pudibunda nucleopolyhedrovirus (DapuNPV) reveals novel genetic connection between baculoviruses
infecting moths of the Lymantridae family. BMC Genomics 16:759, doi 10.1186/
s12864-015-1963-9
Patents
▪
▪
▪
Szewczyk, B., Gromadzka, B. and 11 other
authors. DNA vaccine, method for immunological response induction, antibodies
specifically recognizing hemagglutinin
H5 of influenza virus and application
of DNA vaccine; PL 220281, Published:
29.06.2015
Szewczyk, B., Bieńkowska-Szewczyk, K.
and 4 other authors. Nucleotide sequence of baculovirus polyhedrin gene and
application of the sequence for detection
of different baculoviruses.; PL 212543,
Published : 06.11.2012
Szewczyk, B., Król, E. and 4 other authors.
Uridine derivatives as antiviral agents,
mainly against Flaviviridae family. PL
211936, Published 07.08.2012
▪
▪
▪
▪
The Laboratory closely cooperates with
many European, South American and
Polish scientific groups.
Forest Research Institute in Warsaw
and Biological Control Unit EMBRAPA in
Brazil.
Laboratory of Recombinant Vaccines,
Pharmaceutical Institute in Warsaw,
Silesian Technical University in Gliwice
and MRC in Glasgow.
Institute of Biotechnology and Antibiotics
in Warsaw, Institute of Biochemistry and
Biophysics in Warsaw, National Veterinary Institute in Puławy and our Laboratory.
65
Prof. Krystyna BieńkowskaSzewczyk
Graduated in 1976 at University of
Gdansk, obtained PhD in biochemistry
(1982) at the Faculty of Biology, Geography and Oceanology of University
of Gdansk, habilitation awarded at the
same Faculty in 2002. Full professorship
since 2008. Postdoctoral research: Max
Planck Institute, Tubingen (Germany),
University of California San Francisco
(USA), University of Utah, (USA), The Institute for Animal Science and Health,
(The Netherlands). Since 1998 a partner
in five EU international projects founded by European Framework Programs.
Vice-dean of IFB for 6 years.
Research group
Andrea Lipińska, PhD
Małgorzata Rychlowska, PhD
Michał Rychłowski, PhD
Agnieszka Brzozowska, PhD
Katarzyna Grzyb , PhD
Krzysztof Lacek, PhD
PhD students:
Natalia Derewońko, Mirosława Panasiuk,
Karolina Zimmer, Malgorzata Graul,
Dorota Lesiak
PhD Theses
▪ Alicja Chmielewska „Adenoviruses as
▪
▪
vectors for the construction of a vaccine against hepatitis C virus (HCV)”,
(2013)
Agnieszka Brzozowska „Protein kinase Us3 and glycoprotein E as alpha-herpesvirus cell-to-cell transmission
mediators”, (2013)
Krzysztof Lacek „Characterization
of Ankyrin-repeat Proteins (ANK)
Encoded by Orf virus (ORFV)”, (2015)
66
Viruses that are currently studied in our lab include herpesviruses and hepatitis C virus. We investigate the structure and
functions of envelope glycoproteins and other viral proteins and their interactions with host cells. To understand the
function of viral proteins, we construct live viral mutants
with deleted or modified genes as well as the stable cell
lines expressing the genes of interest. The intramolecular
localization and transport of viral proteins in infected cells is
analyzed by laser confocal microscopy. The construction of
recombinant viral particles labeled with fluorescent markers
allows us to make direct observations of virus multiplication
and spread in live cells.
The examples of research projects include the study of
direct cell-to-cell mode of viral spread which is faster than
entry from outside by free virions. Many viruses ( e.g. HIV)
employ multiple strategies to infect new target cells, exploiting natural junctions between cells as well as stimulating
the formation of new connections. Viruses moving directly from one cell to adjacent cells can avoid being exposed
to the elements of the immunological system. The viral
strains impaired in ability to spread by cell-to-cell transmission are valuable vaccine candidates and the proteins mediating cell-to-cell spread of viruses are essential targets
for antiviral drugs. However, the mechanisms of direct viral
transmission are still poorly understood. We investigate the
role of viral glycoproteins ( gE, gI and others) and protein
kinase Us3 in viral spread, using a wide panel of viral mutants and seeking for cellular partners of viral proteins by
biochemical methods and mass spectrometry.
In other projects we study the mechanism of so called
immune evasion – the strategies used by viruses to avoid
recognition by the immune system of the host. We explore the molecular mechanism of the activity UL49.5 protein, main immunomodulatory protein in some herpesviruses, which downregulates major histocompatibility class I
(MHC I) expression. To identify active amino acid sites and
domains mediating the activity of UL49.5, we use structural studies and protein modeling followed by site-directed
mutagenesis. By using fluorescently labeled cellular target
protein-TAP transporter and shRNA libraries, next generation
sequencing and proteomics we attempt to identify cellular
proteins involved in the mechanism of inhibition. Finally, we
study interactions of UL49.5 with another viral protein – glycoprotein M and cellular trafficking of this protein complex.
In other project we study the role of exosomes, nanosized
vesicles derived from the inner space of a cell, in alphaherpesvirus infection. Exosomes can carry specific cargo (nucleic acids, microRNA, proteins) which may affect the immune response, mediate signaling, promote oncogenesis. We
look for crossroads between exosomes and herpesviruses,
by studying specific incorporation of viral proteins and
microRNA to exosomes.
Hepatitis C virus (HCV) is one of the most dangerous human pathogens and the methods of its control, despite the
recent progress in drug development, are not efficient.
There is no available vaccine to prevent HCV infection. Our
group has been involved in several international projects,
funded by EU Framework Programs, aimed at the development of new strategies of HCV control. In several projects
focused on HCV biology we study structure and function of
hepatitis C glycoproteins , by biochemical and functional
characterization of E1E2 from various genotypes, mutagenesis of the E1 E2 glycoproteins and analysis of recombinant
proteins. We participated in the large project (Hepacivac)
aimed at the development of HCV vaccine and have constructed and characterized numerous adenovirus vectors
expressing HCV envelope glycoproteins. We also produce
these proteins in mammalian cells , baculovirus system and
recently in a novel expression system based on protozoan
Leishmania tarentolae. Using various approaches (siRNA, novel neutralizing antibodies) we also want to investigate cell-to-cell spread of HCV.
Future goals
Our goal is to contribute to better understanding of the
events associated with virus spread in infected organism during infections with viral pathogens, especially the
interaction between viral and cellular factors and the
interaction with host immune response. We plan to work on
the improvement of antiviral neutralizing antibodies which
can be used both for research and for the novel anti-viral
therapies. We also plan to use our expertise in construction of viral vectors for the development of new anti-cancer
therapies.
Our website
www. wirusologia-mwb.cba.pl
Recent publications
▪ Chmielewska A. , Naddeo M , Capo-
▪
▪
▪
ne S ., Ammendola V., Hu K , Meredith L., Verhoye L. , Rychłowska M.,
Rappuoli R, Ulmer JB., Colloca S ,
Nicosia A., Cortese R., Leroux-Roels
G , Balfe P., Bienkowska-Szewczyk
K, Meuleman P., McKeating J. and A.
Folgori (2014) Combined adenovirus
vector and hepatitis C virus envelope
protein prime-boost regime elicits T
cell and neutralizing antibody immune
responses. J. Virol., 88 : 5502-10. doi:
10.1128/JVI.03574-13.
Urbanowicz RA, Lacek K, Lahm A,
Bienkowska-Szewczyk K, Ball JK,
Nicosia A, Cortese R, Pessi A. (2015)
Cholesterol conjugation potentiates
the antiviral activity of an HIV immunoadhesin. J Pept Sci. 21:743-9. doi:
10.1002/psc.2802
Verweij MC, Lipińska AD, Koppers-Lalic
D, Quinten E, Funke J, van Leeuwen HC,
Bieńkowska-Szewczyk K, Koch J, Ressing ME, Wiertz EJ. (2011) Structural
and functional analysis of the TAP-inhibiting UL49.5 proteins of varicelloviruses. Mol Immunol. 48:2038-51.
Brzozowska A., Rychłowski M.,
Lipińska AD., Bieńkowska-Szewczyk K.
(2010) Point mutations in BHV-1 Us3
gene abolish its ability to induce cytoskeletal changes in various cell types
Vet. Microbiol. 143:8-13
▪ Institute of Virology, MRC Glasgow
(Prof. A. Patel)
▪ Okairos company, Italy (Prof. A.Nicosia)
▪ Gent University, Belgium
(Prof. H.Favoreel)
Institute of Molecular and Cell Biology, Warszawa,
Prof. J. Jaworski
▪ International
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 1. Accumulation of herpesviral glycoprotein gE ( fused to GFP) in infected cell
Fig. 2. Cell projections stimulated by expression of Us3 kinase of BHV-1
(bovine herpesvirus)
Fig. 3. GFP- labelled viral particles (green) of BHV-1 moving between cells.
67
Recent Publications
1.
Bednarz-Knoll Natalia, Nastały Paulina, Żaczek Anna, Stoupiec Małgorzata, Riethdorf Sabine, Wikman
Harriet, Müller Volkmar, Skokowski Jarosław, Szade Jolanta, Sejda Aleksandra, Wełnicka-Jaśkiewicz
Marzena, Pantel Klaus. Stromal expression of ALDH1 in human breast carcinomas indicates reduced
tumor progression. Oncotarget 2015, 6(29): 26789-26803 (doi: 10.18632/oncotarget.4628).
2.
Boros-Majewska J., Turczyk Ł., Wei X., Milewski S., Williams D. W. A novel in vitro assay for assessing
efficacy and toxicity of antifungals using human leukaemic cells infected with Candida albicans. Journal
of Applied Microbiology 2015, 119(1): 177-187 (doi: 10.1111/jam.12817).
3.
Chmielewska Alicja M., Rychłowska Małgorzata, Król Ewelina, Solarz Karolina, BieńkowskaSzewczyk Krystyna. Wirusowe zapalenie wątroby typu C - nowe metody leczenia i zapobiegania [Novel
methods of hepatitis C treatment and prevention]. Postępy Higieny i Medycyny Doświadczalnej 2015, 69:
946-963 (doi: 10.5604/17322693.1165197).
4.
Czajkowski Robert, Ozymko Zofia, de Jager Victor, Siwińska Joanna, Smolarska Anna, Ossowicki Adam, Narajczyk Magdalena, Łojkowska Ewa. Genomic, Proteomic and Morphological Characterization of Two Novel Broad Host Lytic Bacteriophages ΦPD10.3 and ΦPD23.1 Infecting Pectinolytic
Pectobacterium spp. and Dickeya spp. PLoS ONE 2015, 10(3): art. no e0119812 (1-23) (doi:10.1371/journal.pone.0119812).
5.
Czajkowski Robert, Ozymko Zofia, Łojkowska Ewa. Application of zinc chloride precipitation method for rapid isolation and concentration of infectious Pectobacterium spp. and Dickeya spp. lytic bacteriophages from surface water and plant and soil extracts. Folia Morphologica 2015 (doi: 10.1007/
s12223-015-0411-1).
6.
Czajkowski Robert, Ozymko Zofia, Siwińska Joanna, Ossowicki Adam, de Jager Victor, Narajczyk
Magdalena, Łojkowska Ewa. The complete genome, structural proteome, comparative genomics and
phylogenetic analysis of a broad host lytic bacteriophage ϕD3 infecting pectinolytic Dickeya spp. Standards in Genomic Sciences 2015, 10: 68 (1-8) (doi: 10.1186/s40793-015-0068-z).
7.
Czajkowski Robert, Perombelon M. C. M., Jafra Sylwia, Łojkowska Ewa, Potrykus Marta,
van der Wolf Jan M., Śledź Wojciech. Detection, identification and differentiation of Pectobacterium and Dickeya species causing potato blackleg and tuber soft rot: a review. Annals of Applied
Biology 2015, 166(1): 474-487(doi: 10.1111/aab.12166).
8.
Czajkowski Robert, van der Wolf Jan M., Królicka Aleksandra, Ozymko Zofia, Narajczyk Magdalena,
Kaczyńska Natalia, Łojkowska Ewa. Salicylic acid can reduce infection symptoms caused by Dickeya
solani in tissue culture grown potato (Solanum tuberosum L.) plants. European Journal of Plant Pathology
2015, 141(3): 545-558 (doi: 10.1007/s10658-014-0561-z).
9.
Czapiewski Piotr, Wełnicka-Jaśkiewicz Marzena, Seroczyńska Barbara, Skokowski Jarosław, Sejda Aleksandra,
Szade Jolanta, Wiewiora Claudia, Biernat Wojciech, Żaczek Anna. CD99 correlates with low cyclin D1,
high topoisomerase 2α status and triple negative molecular phenotype but is prognostically irrelevant in
breast carcinoma. Polish Journal of Pathology 2015, 66(3): 269-275 (doi: 10.5114/pjp.2015.54961).
10.
Englund Emelie, Reitsma Bart, King Ben C., Escudero-Esparza Astrid, Owen Sioned, Orimo Akira, Okrój
Marcin, Anagnostaki Lola, Jiang Wen G., Jirström Karin, Blom Anna M. The human complement inhibitor
Sushi Domain-Containing Protein 4 (SUSD4) expression in tumor cells and infiltrating T cells is associated
with better prognosis of breast cancer patients. BMC Cancer 2015, 15: art. no: 737 (1-13) (doi: 10.1186/
s12885-015-1734-7).
11.
Glaza Przemysław, Osipiuk Jerzy, Wenta Tomasz, Zurawa-Janicka Dorota, Jarząb Mirosław, Lesner Adam,
Banecki Bogdan, Skórko-Glonek Joanna, Joachimiak Andrzej, Lipińska Barbara. Structural and functional analysis of human HtrA3 protease and its subdomains. PLoS ONE 2015, 10(6): art. no e0131142 (1-24)
(doi: 10.1371/journal.pone.0131142).
68
12.
Golanowska Małgorzata, Galardini M., Bazzicalupo M., Hugouvieux-Cotte-Pattat Nicole, Mengoni
Alessio, Potrykus Marta, Sławiak Monika, Łojkowska Ewa. Draft genome sequence of highly virulent strain of the plant pathogen Dickeya solani, IFB0099. Genome Announcements 2015, art. no e0010915 (1-2) (doi: 10.1128/genomeA.00109-15).
13.
Gołuński Grzegorz, Borowik Agnieszka, Wyrzykowski Dariusz, Woziwodzka Anna, Piosik Jacek.
Pentoxifylline as a modulator of anticancer drug doxorubicin. Part I: reduction of doxorubicin DNA binding. Chemico-Biological Interactions 2015, 242: 291-298 (doi: 10.1016/j.cbi.2015.10.008).
14.
Grabowski Michał, Banecki Bogdan, Kadziński Leszek, Jakóbkiewicz-Banecka Joanna,
Kaźmierkiewicz Rajmund, Gabig-Cimińska Magdalena, Węgrzyn Grzegorz, Węgrzyn Alicja,
Banecka-Majkutewicz Zyta. Genistein inhibits activities of methylenetetrahydrofolate reductase and lactate dehydrogenase, enzymes which use NADH as a substrate. Biochemical and Biophysical Research
Communications 2015, 465(3): 363-367 (doi: 10.1016/j.bbrc.2015.08.004).
15.
Grinholc Mariusz. Comments on „Biofilms of Candida albicans serotypes A and B differ in their sensitivity
to photodynamic therapy”. Lasers in Medical Science 2015, 30(8): 2221 (doi: 10.1007/s10103-014-1591-7).
16.
Grinholc Mariusz, Nakonieczna Joanna, Fila Grzegorz, Taraszkiewicz Aleksandra, Kawiak
Anna, Szewczyk Grzegorz, Sarna Tadeusz, Lilge Lothar, Bielawski Krzysztof P. Antimicrobial photodynamic therapy with fulleropyrrolidine: photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies. Applied Microbiology and Biotechnology 2015, 99(9): 4031-4043 (doi: 10.1007/
s00253-015-6539-8).
17.
Grinholc Mariusz, Rodziewicz Aleksandra, Foryś Katarzyna, Rapacka-Zdończyk Aleksandra, Kawiak Anna, Domachowska Anna, Gołuński Grzegorz, Wolz Christiane, Mesak Lili, Becker
Karsten, Bielawski Krzysztof P. Fine-tuning recA expression in Staphylococcus aureus for antimicrobial photoinactivation: importance of photo-induced DNA damage in the photoinactivation mechanism.
Applied Microbiology and Biotechnology 2015, 99(21): 9161-9176 (doi: 10.1007/s00253-015-6863-z).
18.
Ilk Nadine, Ding Jia, Ihnatowicz Anna, Koornneef Maarten, Reymond Matthieu. Natural variation for
anthocyanin accumulation under high-light and low-temperature stress is attributable to the enhancer
of AG-4 2 (HUA2) locus in combination with production of anthocyanin pigment1 (PAP1) and PAP2. New
Phytologist 2015, 206(1): 422-435 (doi: 10.1111/nph.13177).
19.
Kadziński Leszek, Prokopowicz Magdalena, Jakóbkiewicz-Banecka Joanna, Gabig-Cimińska Magdalena, Łukasiak Jerzy, Banecki Bogdan. Effect of Silicone on the Collagen Fibrillogenesis and Stability.
Journal of Pharmaceutical Sciences 2015, 104(4): 1275-1281 (doi: 10.1002/jps.24351).
20.
Koper Tomasz, Polit Agnieszka, Sobiecka-Szkatula Anna, Węgrzyn Katarzyna, Scire Andrea, Figaj
Donata, Kadziński Leszek, Zarzecka Urszula, Żurawa-Janicka Dorota, Banecki Bogdan, Lesner Adam,
Tanfani Fabio, Lipińska Barbara, Skórko-Glonek Joanna. Analysis of the Link between the Redox State and
Enzymatic Activity of the HtrA (DegP) Protein from Escherichia coli. PLoS ONE 2015, art. no e0117413 (124) (doi: 10.1371/journal.pone.0117413).
21.
Kosikowska Paulina, Pikula Michał, Langa Paulina, Trzonkowski Piotr, Obuchowski Michał, Lesner Adam.
Synthesis and Evaluation of Biological Activity of Antimicrobial – Pro-Proliferative Peptide Conjugates.
PLoS ONE 2015, 10(10): art. no e0140377 (1-16) (doi: 10.1371/journal.pone.0140377).
22.
Koszałka Patrycja, Gołuńska Monika, Stanisławowski Marcin, Urban Aleksandra, Stasiłojć
Grzegorz, Majewski Marceli, Wierzbicki Piotr, Składanowski Andrzej C., Bigda Jacek. CD73 on
B16F10 melanoma cells in CD73-deficient mice promotes tumor growth, angiogenesis, neovascularization, macrophage infiltration and metastasis. International Journal of Biochemistry & Cell Biology 2015,
69: 1-10 (doi: 10.1016/j.biocel.2015.10.003).
23.
Krejmer Martyna, Skrzecz Iwona, Wasąg Bartosz, Szewczyk Bogusław, Rąbalski Łukasz.
The genome of Dasychira pudibunda nucleopolyhedrovirus (DapuNPV) reveals novel genetic connection
between baculoviruses infecting moths of the Lymantriidae family. BMC Genomics 2015, 16(1): 759 (1-13)
(doi: 10.1186/s12864-015-1963-9).
24.
Lager Ida, Głąb Bartosz, Eriksson Lovisa, Chen Guanqun, Banaś Antoni, Stymne Sten. Novel reactions
in acyl editing of phosphatidylcholine by lysophosphatidylcholine transacylase (LPCT) and acyl-CoA:glycerophosphocholine acyltransferase (GPCAT) activities in microsomal preparations of plant tissues.
69
Planta 2015, 241(2): 347-358 (doi: 10.1007/s00425-014-2184-1).
25.
Lilla Roland, Dutkiewicza Rafał, Freiberta Sven A., Heidenreicha Torsten, Mascarenhasa Judita, Netza
Daili J., Paula Viktoria D., Pierika Antonio J., Richtera Nadine, Stümpfiga Martin, Srinivasana Vasundara,
Stehlinga Oliver, Mühlenhoff Ulrich. The role of mitochondria and the CIA machinery in the maturation
of cytosolic and nuclear iron-sulfur proteins. European Journal of Cell Biology 2015, 94(7-9): 280-291 (doi:
10.1016/j.ejcb.2015.05.002).
26.
Łepek Krzysztof, Pająk Beata, Rąbalski Łukasz, Urbaniak Kinga, Kucharczyk Krzysztof, MarkowskaDaniel Iwona, Szewczyk Bogusław. Analysis of coinfections with A/H1N1 strain variants among pigs in
poland by multitemperature single-strand conformational polymorphism. BioMed Research International
2015, 2015: art. no 535908 (doi: 10.1155/2015/535908).
27.
Łodyga-Chruścińska Elżbieta, Symonowicz Marzena, Sykuła Anna, Bujacz Anna, Garribba Eugenio, Rowińska-Żyrek Magdalena, Ołdziej Stanisław, Klewicka Elżbieta, Janicka Magdalena, Królewska Karolina,
Cieślak Marcin, Brodowska Katarzyna, Chruścinski Longin. Chelating ability and biological activity of hesperetin Schiff base. Journal of Inorganic Biochemistry 2015, 143: 34-47 (doi: 10.1016/j.jinorgbio.2014.11.005).
28.
Maszota Martyna, Karska Natalia, Spodzieja Marta, Ciarkowski Jerzy, Kołodziejczyk Aleksandra S.,
Rodziewicz-Motowidło Sylwia, Czaplewska Paulina. Structural studies of the C-terminal 19-peptide of
serum amyloid A and its Pro→Ala variants interacting with human cystatin C. Journal of Molecular Recognition 2015, 28(7): 413-426 (doi: 10.1002/jmr.2457).
29.
Miękus Natalia, Olędzka Ilona, Plenis Alina, Woźniak Zofia, Lewczuk Anna, Koszałka Patrycja, Seroczyńska
Barbara, Bączek Tomasz. Gel electrophoretic separation of proteins from cultured neuroendocrine tumor
cell lines. Molecular Medicine Reports 2015, 11(2): 1407-1415 (doi: 10.3892/mmr.2014.2864).
30.
Moskot Marta, Jakóbkiewicz-Banecka Joanna, Smolińska Elwira, Banecki Bogdan, Węgrzyn Grzegorz,
Gabig-Cimińska Magdalena. Activities of genes controlling sphingolipid metabolism in human fibroblasts
treated with flavonoids. Metabolic Brain Disease 2015, 30(5): 1257-1267 (doi: 10.1007/s11011-015-9705-x).
31.
Moskot Marta, Jakóbkiewicz-Banecka Joanna, Kloska Anna, Smolińska Elwira, Mozolewski Paweł,
Malinowska Marcelina, Rychłowski Michał, Banecki Bogdan, Węgrzyn Grzegorz, Gabig-Cimińska
Magdalena. Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome
biogenesis by flavonoids. Scientific Reports 2015, 5: art. no 9378 (1-13) (doi: 10.1038/srep09378).
32.
Niedźwiecka Natalia, Grzyb Katarzyna, Nona-Mołdawa Agnieszka, Gronczewska Jadwiga, Skorkowski
Edward F. Purification and stability of octameric mitochondrial creatine kinase isoform from herring
(Clupea harengus) organ of vision. Comparative Biochemistry and Physiology B-Biochemistry & Molecular
Biology 2015, 185: 16-23 (doi: 10.1016/j.cbpb.2015.03.002).
33.
Piasecka Dominika, Składanowski Andrzej C. , Kordek Radzisław, Romańska Hanna M., Sądej Rafał.
Aspekty regulacji aktywności receptora progesteronu (PR) - znaczcenie w progresji raka gruczołu piersiowego [Aspects of progesterone receptor (PR) activity regulation - impact on breast cancer progression].
Postępy Biochemii 2015, 61(2): 198-206
34.
Pikora Mateusz, Giełdoń Artur. RASMOL AB - New functionalities in the program for structure analysis.
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Important Dates and Facts
2015 The completion of the construction of the new Institute of Biotechnology building
2015 Prof. Krzysztof Bielawski re-elected Vice-President of Scanbalt
2015 XXI edition of the Summer Biotechnology School organized by IFB
2015 Establishing of IFB Sientific Advisory Board
2014 25 April - laying of the cornerstone for the new biotechnology building at University of Gdansk Campus of the
construction of the new building of the Institute of Biotechnology at University of Gdańsk Campus
2014 XX edition of the Summer Biotechnology School organized by IFB
2014 Establishing the units of Core Facility Laboratories and Teaching Laboratories at IFB
2013 Establishing of a new unit at IFB dedicated to facilitating research management & administration:
Dean’s Office for Research and Project Management
2013 Start of the FP7 project MOBI4Health - CENTRE OF MOLECULAR BIOTECHNOLOGY FOR HEALTHY LIFE
Biotech solutions bringing health to living organisms and environment supported by mass spec-focused research platform” (2013-2016, 7. Framework Programme of the European Union), coordination
by Prof. Krzysztof Bielawski
2013 XX Anniversary of IFB
2012 Funding from the National Centre for R&D for the construction of a new building of the Institute of
Biotechnology obtained (EU Structural Funds).
2012 Consortium agreement between IIMCB (Warsaw) and IFB signed
2012 IFB again receives funding for the so-called commissioned study programmes and for improving the alumnis’
opportunities on the labour market
2012 Biotechnology at IFB as one of the best study courses receives additional funding from the Ministry for Science
and Higher Education for further improving the study programme
2012 Distinction for the Best Major for the study course Biotechnology at IFB granted by the Ministry for Science
and Higher Education
2011 Distinction for the study course Biotechnology (B.Sc. and M.Sc.) at IFB granted by the Polish Accreditation
Committee
2011 Establishing of IFB Advisory Council to intensify cooperation with institutions and companies from the
biotech sector
2011 International Institute of Molecular and Cell Biology in Warsaw (IIMCB) joins the Life Sciences and Mathematics
Interdisciplinary Doctoral Studies (LiSMIDoS)
2010 IFB obtains the first category in the National Evaluation of Scientific Institution (tor the 3rd time) and is ranked
in the 1 st place within the group of biology at Polish universities
2010 Prof. Ewa Łojkowska is elected vice-chairwoman of the ScanBalt Association
2010 The Central Commission for Scientific Titles and Degrees licenses the Faculty to confer habilitation in biological
sciences in the discipline of biochemistry
2010 Establishing of Life Sciences and Mathematics Interdisciplinary Doctoral Studies (LiSMIDoS)
2010 Opening of the International Doctoral Project, financed by the Polish Science Foundation from the Innovative
Economy Programme, EU Structural Funds, coordination by Prof. Jarosław Marszałek
2010 IFB obtains the premium category in the National Evaluation of Scientific Organizations
2009 IFB is funded by Ministry of Science and Higher Education within the frame of Commissioned fields of
studies in Polish universities under the Human Capital Program, EU Structural Funds, coordination by
Prof. Igor Konieczny.
79
2008 Start of collaboration and exchange activities for Master degree students with the University of Chicago, USA
and University of Virginia, USA
2007 IFB is granted with accreditation for teaching biotechnology by the Polish University Accreditation
Commission (for the 2nd time)
2006 IFB becomes partner in the INTERREG III project ScanBalt Campus (2006-2008). The Centre of Knowledge on
Molecular Diagnostics for Medicine, Plant and Animal Diseases in Gdańsk, coordination by Prof. Ewa Łojkowska
and Prof. Jacek Bigda
2006 Prof. Krzysztof Liberek elected as member of the European Molecular Biology Organization
2005 IFB is granted the accreditation for teaching biotechnology granted by the State Accreditation Commission
2005 Opening of new laboratories belonging to the Faculty at the Medical University of Gdańsk (Tricity Academic
Experimental Animal House – Research Service Centre of the Medical University of Gdańsk)
2005 IFB obtains the first category in the National Evaluation of Scientific Institution (for the 2nd time)
2003 IFB establishes the Centre of Excellence BioMoBiL – Centre of Bio-safety Research and Molecular Biomedicine
– Integration in Education and Research Towards the Knowledge and Technology Transfer Level (2003-2006, 5.
Framework Programme of the European Union); coordination by Prof. Jacek Bigda and Prof. Ewa Łojkowska.
2002 IFB is granted with accreditation for teaching biotechnology by the Polish University Accreditation Commission
2001 IFB becomes member of the ScanBalt association. Prof. Anna Podhajska elected as vice-chairwoman of ScanBalt
(2001-2005)
2001 IFB obtains first category in the National Evaluation of Scientific Institutions
2001 The Faculty becomes a partner in the consortium of 10 European Universities and participates in the establishment of a new teaching program: Job Creation Biotechnology Diploma – International First Level Degree
(3 years), coordinated by prof. Mariapia Viola Magni from Universita degli Studi di Perugia, Italy
2000 Prof. Wacław Szybalski is granted the title of Doctor Honoris Causa of the Medical University of Gdańsk.
The initiative comes from and is supervised by the IFB. Prof. Wacław Szybalski is also honoured at the Marie
Curie-Skłodowska University of Lublin (1980) University of Gdańsk (1989) and Technical University of Gdańsk
(2002)
1999 Opening of new laboratories in the Institute of Biotechnology, UG. Main lecture hall named in the memory of
late prof. Karol Taylor, the founder of molecular biology in Gdańsk
1999 Central Commission for Scientific Titles and Degrees licenses IFB to confer PhD degrees in biological sciences
in the discipline of biochemistry
1994 Successful application for a first EU project: Creation and development of a novel Faculty of Biotechnology
(TEMPUS, 1994-1997), coordination by Prof. Wiesław Makarewicz, Dean of IFB
1994 1st Biotechnology Summer School organized at Wilga, near Warsaw, by Prof. Anna Podhajska. Prof. Wacław
Szybalski is the honorary guest at the event
1993 Senate of the Medical University of Gdańsk and Senate of the University of Gdańsk decide to establish
the Intercollegiate Faculty of Biotechnology UG & MUG
1992 Crystallization of the idea to create a joint unit for teaching biochemistry among the universities in Gdańsk.
Rectors of the University of Gdańsk, Medical University of Gdańsk and Technical University of Gdańsk appoint
Prof. Anna J. Podhajska as the person responsible for organizing and establishing the structure of this faculty
80
Intercollegiate Faculty of Biotechnology of University
of Gdańsk and Medical University of Gdańsk
Antoniego Abrahama 58, 80-307 Gdańsk, Poland
www.biotech.ug.edu.pl

Report 2015 - Mobi4Health

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