Date : 03/02/2011

Laboratory
Groupe Imagerie et Modélisation
URA 2582 - Institut Pasteur
25 rue du Docteur Roux 75015 Paris
Director : Christophe ZIMMER

PhD Supervisor
Christophe ZIMMER
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 40 61 38 91

Subjects
1.: super-resolution microscopy
2.: single molecule imaging
3.: chromatin, HIV

Tools-Methodologies:
1.: image processing
2.: optics and electronics
3.: chemistry

Summary of lab's interests

Our group develops computational imaging and modeling techniques to gain a quantitative understanding of cell biological processes. We combine approaches from applied mathematics, physics and cell biology, either within the group or through collaborations. We develop computational methods to extract massive and high accuracy information from imaging data, which we use to constrain and test physics based models. We are also actively interested in developing advanced light microscopy methods, particularly super-resolution microscopy (see below). Our current work focuses on the spatial organization and dynamics of genes and chromosomes inside the nuclear volume and on the replication cycle of HIV.

Summary of project

Light microscopy is an invaluable tool in biology, but has traditionally been limited by the diffraction limit of resolution, which is two orders of magnitude larger than typical molecular scales. Over the last years, several new microscopy techniques have emerged, that increase resolution by up to an order of magnitude. This still leave a gap of another order of magnitude to reach truly molecular-scale imaging. Our laboratory has implemented a PALM/STORM super-resolution microscope, based on computational localization of single molecules, which can achieve ~20-30 nm resolution and is successfully used in a large number of biological projects. The goal of this PhD project is to improve resolution to the single nanometer scale. This goal will be addressed by combining techniques from optics, electronics, statistical image processing, and chemistry. Targeted biological applications include the analysis of chromatin structure, the plasticity of nuclear pores, and dissection of the HIV replication cycle.

Interdisciplinarity of the project

This project is highly interdisciplinary, since improving resolution will require techniques from applied mathematics and statistics (to design rigorous and reliable molecule localization algorithms), optics (to optimize the light path and maximize signal-to-noise ratio) and chemistry (the number of photons emitted by molecules, which determines resolution, critically depends on the chemical conditions in the sample).

Available funding for this project : several grant applications are pending