Date : 03/02/2011

Laboratory
Theoretical Modeling of Cellular Physiology
UMR 8542
Ecole Normale Supérieure
46 rue d'Ulm 75005 Paris
Director : David HOLCMAN

PhD Supervisor
David HOLCMAN
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 44 32 36 61

Subjects
1.: heart
2.: modeling
3.: data analysis

Tools-Methodologies:
1.: modeling, simulations
2.: data analysis
3.: engineering

Summary of lab's interests

The main interest of our group is to study the function of cellular microstructures in cellular biology and to develop related modeling tools. Our goal is to identify principles underlying cellular and network function in normal and pathological conditions. For that purpose, in collaboration with experimental groups, we aim to answer basic questions in cellular biology such as what defines trafficking in cells, how cells respond to stimuli, what makes virus particles optimal. We are currently working on the nucleus organization, cytoplasmic viral trafficking and synapses. Recently using asymptotic analysis and Brownian simulations, we estimated the synaptic current at excitatory synapses and study the effect of the cleft geometry, receptor trafficking and other factors.

Summary of project

Atrial fibrillation (AF) is the most common cardiac arrhythmia (abnormal heart rhythm). Instead of a coordinated contraction, the heart muscles of the atria are not working in synchrony. In AF, the normal electrical> impulses that are generated by the sinoatrial node are overwhelmed by disorganized electrical impulses that originate in the atria and pulmonary veins, leading to conduction of irregular impulses to the ventricles that generate the heartbeat. The result is an irregular heartbeat which may occur in episodes lasting from minutes to weeks, or it could occur all the time for years. The natural tendency of AF is to become a chronic condition. Chronic AF leads to an increase in the risk of death and stroke. The simulations could be used to diagnose early signs of AF, so that early decision could be taken at the medical level. Thus their approach will allow for the development of useful new therapeutic approaches.

Interdisciplinarity of the project

The goal of this project is to bring together one hand the groups of Pr. A. Cohen , cardiologist from Hosp. St Antoine (Paris, France), which has accumulated an expertise in AF, having collected a pool of data about AF and on the other hand, the group of mathematical modeling of Pr. D. Holcman, specialized in applied mathematics, biophysical modeling, random stochastic dynamical systems and numerical simulations. The goal of this phd is to extract and combine clinical and biological parameters, to define dynamics of key variables and to generate a mathematical model that can predict the transition from normal to AF. The candidate will validate the approach using the data base of Pr Cohen and to finalize the approach, he/she will have to participate in generating a software that could predict and monitor via Web applications the evolution of various parameters leading to AF.