Revision as of 19:21, 22 September 2013

Project What are PCBs ? Overview Modeling Achievements

Modeling

"La modélisation, c'est comme le sexe, plus y'a d'inconnues, plus c'est chaud." ---qui a dit ça

Before you start, maybe those words could make you understand more quickly our project.

What do we model?

This modeling is about the simulation of FNR aero/anaerobic regulation system which we have successfully achieved in our experiments. The second part of our experiment: the PCBs sensor system is not touched in the modeling.

The FNR aero/anaerobic regulation system, briefly, we try to rebuild mathematically a system which can simulate the alternate expression of FNR in aerobic or anaerobic situation, from the translation of fnr to the production of reporter protein.

What’s our purpose for this modeling?

The main aim of our modeling is recreate the aero/anaerobic reporter protein expression system. By alternating the oxygen concentration, activated or inactivated FNR combine (or not) with potential sensor gene sequence and make blue or red color. Our job is to see if we can observe the alternating red and blue curve when we change the oxygen condition.

How do we modeling?

As the research of FNR regulation system is a well-studied territory, we found some excellent scientific paper in library especially “Regulation of Aerobic to Anaerobic Transitions by the FNR cycle in Escherichia coli” by Dean A.Tolla and Michael A.Savageau. They have successfully reproduced the FNR cycle by using differential equation system. And in our modeling we decided to redo what they have done but use a different method: a stochastic system created by new modeling tool: Hsim. Hsim is a stochastic automation simulator, it simulate chemical or enzymatic reactions between molecules and based on reactions it can simulate whole system.

What is our chanllenge??on met ou pas??

constructing

Modeling of oxygen sensing system

We represent the oxygen sensing system by FNR. This biological system was already studied by http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867928/ and we follow their modelisation in 3 steps. We have chose HSIM, a multi-agents programme developped at our university in order to follow the assembly, movements and dissociation of a large number of molecules in a virtual cell. HSIM replaces the Ordinary Differential Equations and mimics chemical reactions of the real system by rewriting rules. Following our modelisation process, we provided the list of molecules, the rewriting rules, and the initial values of each molecule quantity in a configuration file to HSIM. We also have developed a web version of HSIM.

Steps of modeling

1rst step: from the biological knowledges toward the functional scheme

cf. scheme https://docs.google.com/drawings/d/1wDKOasknJ_pjbEbQdGmE_qBtWNujOnoDIkDVmNso1KM/edit

2nd step: from functional scheme toward equations system

We provide 2 web versions of the HSIM simulator. Each of them implements a different set of rules. The "Simple simulation" describes the following reactions: - translation of Pfnr gene into FNR protein (FNR without Fe) - dimerisation of 4Fe-FNR (action of Ise protein) - oxydation: in aerobic conditions, oxygen inactivates FNR but cell continues to reactivate it (action of Ise protein) - degradation of each kind of FNR (FNR without Fe, FNR activated, and FRN inactivated), a green protein, and a red protein (action of ClpXP protein) - activation/inactivation of a gene under a repressor promotor (green) and production or not of the cognate protein - activation/inactivation of a gene under an activator promotor (red) and production or not of the cognate protein

We used the simple simulation to explore different combinations of initial values. The complex simulation itemizes more rules than the simple simulation. In particular it contains ...

Here you will find our configuration files to launch HSIM: links towards the configuration files.

===3rd step: HSim on a web simulator=== Damir has conceived and implemented the web simulations

==How to launch the simulations?== When simulation is launched, curve of molecule quantities appear with time. The "START/PAUSE" and "RESET" buttons give control to the simulation time. You may change the oxygen quantities with the "O2" panel.

Results and discussion

en cours

Oxygen sensing system

Simple simulation

Loading simulation...

Complex simulation