PhD PROPOSAL FOR THE PASTEUR-PARIS UNIVERSITY INTERNATIONAL PROGRAM

 

Deadline for full application: December 15th, 2013

 

Interviews: March, 2014

Start of the Ph.D.: October 1st, 2014

 

 

 

Department: Virology

Title of the PhD project: Molecular and cellular mechanisms of retroviral particles formation and transmission via cell contacts

Name of the lab: Structural Virology Unit, “ Cell dynamics and viral transmission” Team

Head of the lab: F.A. REY

PhD advisor: M.-I. THOULOUZE

Email address: marie-isabelle.thoulouze@pasteur.fr

Web site address of the lab:

Doctoral school affiliation and University: Physiologie et Physiopathologie, Université Paris 6.

(To be redefined)

 

Presentation of the laboratory and its research topics:

Our group is part of the Structural Virology Unit headed by Félix Rey, in the Department of Virology. In addition to its leading expertise in Structural virology, the unit brings together scientists with different areas of expertise including Cell biology of viral infections.

Ongoing work of our group is focused on studying virus transmission via cell-cell contacts, with a particular interest in human retroviruses transmission between T lymphocytes. We recently discovered a new mode of virus transmission involving viral biofilms and occuring through transient intercellular contacts between infected cells and target cells (1, 2).

 

Description of the project:

Scientific background: Junctions formed by T lymphocytes may be subverted by human retroviruses (HIV-1 and HTLV-1) to escape immune responses and to disseminate into its host. Recent studies by our group and others, have shown that HIV-1 and HTLV-1 infection of T lymphocytes impairs their capacity to form immune synapses, specialized junctions between T lymphocytes and antigen presenting cell triggering T cell activation (3). Moreover, human retroviruses use some cellular mechanisms involved in the formation of immune synapses to generate contacts between infected and target T lymphocytes, promoting direct cell to cell spread (named virological synapses) , which represents the major mode of retroviral transmission (4). Thus, human retroviruses may modulate T lymphocyte properties and reshape the formation of intercellular junctions between infected T lymphocytes and other immune cells, that are key for immune responses and virus spread.

Objectives : The goal of this project is to elucidate the role of a BAR-domain containing protein during retrovirus infection. This protein, whose expression is drastically modulated by both HIV-1 and HTLV-1 infection, is a multifunctional protein known to interact with cell membranes, sensing membrane curvature, but also with many regulators of actin cytoskeleton network. By regulating cortical tension and intracellular traffic, it is involved in the formation of epithelial cell junction and in cell migration. Its role in T lymphocyte biology is largely unknown. Our recent data, using RNA interference, revealed a key role of this protein in T cell cortical tension and in immune synapses stability (unpublished data), suggesting that this cellular factor could be important for viral particle morphogenesis and/or viral transfer via cell contacts (nature and/or dynamics of contacts).

This project, at the interface between virology and cell biology, will use advanced microscopy techniques on live cells along with molecular biology, cell biology and biophysics approaches.

 

References:

1. Pais-Correia et al. Nature Medicine 2010; Thoulouze et al. Trends in Microbiology 2011

3. Thoulouze et al. Immunity 2006

4. Sol-Foulon et al. EMBO Journal 2007

 

Keywords: Virology, Cell biology, Virus transmission, Human retroviruses, T lymphocyte, cell junctions, cell dynamics, Human Immunodeficiency Virus Type 1 (HIV-1), Human T cell Leukemia Virus type 1 (HTLV-1).

 

Expected profile of the candidate: We are looking for a motivated and talented student interested in understanding fundamental aspects of virology and cell-cell communication. The successful candidate will have the opportunity to learn various scientific and technical expertises and to interact with leading researchers in the field.

 

Contact: Maria-Isabel Thoulouze, PhD, HDR.  Email: marie-isabelle.thoulouze@pasteur.fr

Mis à jour le 16/09/2013