Date : 10/02/2012

Laboratory
Group of computationaional biology and Applied Mathematics
IBENS, Ecole normale Superieure
46 rue d'Ulm
75005 Paris
Website
Main discipline : Biophysics
Lab 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.: Analysis of superresolution trajectories
2.: HIV trafficking in cells
3.: Host-virus interactions

Tools and Methodologies
1.: acquisition of trajectories
2.: data analysis
3.: modeling, simulations

Summary of lab's interests
The main interest of my group is to study the function of microdomains in cellular biology and to develop physical modeling, mathematical analysis, numerical simulations and novel methods for data analysis. Our goal is to identify principles underlying cellular and network function in normal and pathological conditions.

Summary of project
Lentiviruses such as the Human Immunodeficiency Virus (HIV) have evolved the ability to pass through the nuclear pore of infected cells to reach its site of genome replication, the nucleus. When it passes through the nuclear pore, the virus is already a reduced version of the infectious virion that entered cell: for instance, it no longer contains viral envelope, matrix or capsid. However the genome does not cross the nuclear pore as a naked nucleic acid, it is still associated with proteins that are required for nuclear import and/or integration, and the complex is referred to as pre-integration complex (PIC) (Fassati, 2006; Arhel, 2010). HIV passage through the nuclear pore is a kinetic bottleneck for infection. These kinetic challenges could constitute points of weakness in the viral replication cycle and we would benefit greatly from a greater understanding of their nature. We propose to combine single particle trajectories with biophysical modeling and novel stochastic analysis to extract various features of HIV trafficking such as the dynamics, the motion along microtubules, Actin filaments,.... D. Holcman's group has developed novel stochastic approach to extract biophysical information from combining super-resolution microscopy data.The group of N. Arhel will be testing a new super-resolution microscope that will provide novel working material.

Interdisciplinarity of the project
This project is 50 % in my group and 50 % in the group of Dr. N. Arhel (Pasteur), to collect and analyze data.