plakat - PL-Grid

Negative feedback based organized systems simulations
Jakub Wach3, Marian Bubak1,3, Leszek Konieczny2, Irena Roterman-Konieczna2
University of Science and Technology, Department of Computer Science, Kraków, Poland
2Jagiellonian University, Department of Bioinformatics and Telemedicine, Kraków, Poland
3Academic Computer Centre Cyfronet AGH, Kraków, Poland
1AGH
Problem description
•
•
•
•
Bio-systems are enormously complex (around 220x10^9 cells in a human body)
Current simulation models are insufficient
Simulation of bio-system is the way for modern medicine
• Faster development of new drugs
• Insight into origins and development of diseases
Needs to take into account system as a whole – multiple levels of organization
Proposed solution
•
•
•
Use simplest regulator – negative feedback
inhibition system (NFIS) as a building block
Connect NFISs using relations analogous to those
observed in vivo
Construct a functional proteome of a bio system
(instead of depicting a static structure)
System structure
Single NFIS
• Effector – delivers a product
• Receptor – disables Effector once product’s
concentration reaches active threshold
Cooperation relation
• One NFIS delivers substrate to another,
controlling its production
• Example – enzymatic cascade, where a
substance is passed between enzymes
Coordination relation
• Product of one NFIS can activate Receptor of an
other NFIS
• Example – allosteric control of enzymes
External receptor relation
• One NFIS can order other NFIS to change its
threshold
• Example – hormonal contol of cells
Results and future work
• Simulation - http://crick.cm-uj.krakow.pl:8080/nfs
 Implements discreet simulation algorithm
 Allow users to define Organized Systems (OS)
composed of NFISs
 Provides users with easy-to-use structure and
parameters editors
• Results
 Simulation of even simple OSs display complex
behaviour
 Will allow researchers to discover emergent
properties of simulated bio systems
 Building a workflow utilizing the simualtion core will
automate and speed-up search
1. Leszek Konieczny, Irena Roterman-Konieczna, Paweł Spólnik, Systems Biology: Functional Strategies of Living Organisms, Springer
Dordrecht, New York, London 2013
2. Karr, Jonathan R. et al., A Whole-Cell Computational Model Predicts Phenotype from Genotype, Cell , Volume 150 , Issue 2
This study was partially supported by PLGrid Core project no POIG.02.03.00-12-137/13
INNOVATIVE
ECONOMY
NATIONAL
COHESION
STRATEGY
EUROPEAN UNION
EUROPEAN
REGIONAL
DEVELOPMENT
FUND
The work was co-funded
by the European Regional
Development Fund as part
of the Innovative Economy
program.