Date : 27/02/2011

Laboratory
Membrane dynamics and Intracellular Traffic
UMR 7592-Institut Jacques Monod CNRS
Université Paris Diderot
Bât.Buffon - 15 rue Hélène Brion
75205 PARIS
Director : Catherine Jackson
Main discipline : Cell Biology
Website : http://www.lebs.cnrs-gif.fr/jackson/jackson_eng.html currently;
the Jackson group will move to the IJM in June, 2011: http://www.ijm.fr/ijm/institut/presentation/

PhD Supervisor
Catherine Jackson
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 69 82 34 91

Subjects
1.: Membrane curvature sensors
2.: Vesicular trafficking
3.: Biomolecular engineering

Tools and methodologies
1.: Live cell imaging/FRET/TIRF microscopy and cell culture
2.: Design and purification of bioprobes
3.: Liposome binding assays (Fluorescence, flotation)

Available funding for this project
My group currently has funding from the ANR and FRM, and Bruno Antonny has been awarded a highly competitive ERC Advanced Grant.

Summary of lab's interests

C. Jackson's laboratory studies the molecular mechanisms of membrane trafficking in eukaryotic cells. Our studies have focused on the trafficking pathways regulated by the small G protein Arf1, and its activators and effectors. In collaboration with the laboratory of B. Antonny, we have been studying the role of amphipathic membrane curvature sensors, originally identified in regulators and effectors of Arf1 by the Antonny group. These fascinating proteins can distinguish different types of membranes based on their shape, binding specifically to highly curved membranes such as those of transport vesicles. We have discovered and are currently studying a novel Arf1-dependent trafficking pathway between the endoplasmic reticulum and lipid droplets, revealing a close connection between membrane trafficking and lipid homeostasis, with important implications for human diseases such as metabolic syndrome and diabetes. Finally, we are fascinated by the ways in which intracellul ar pathogens such as poliovirus and Hepatitis C virus subvert Arf1-dependent membrane trafficking pathways of cells for their own purposes.

Summary of project

A eukaryotic cell is characterized by its internal membrane compartmentalization. The primordial event that gave rise to the first eukayotic cell was the separation of the endoplasmic reticulum (ER)-nuclear envelope membrane system from the plasma membrane (PM). This compartmentalization permitted eukaryotic cells to develop a wide range of forms and functions, important for the development of complex multicellular organisms. Compartmentalization also created the need for communication between the different membrane-bound organelles, which is mediated by small membrane-bound transport vesicles. Cells use cycles of vesicle budding and fusion for dynamic exchange of material between organelles, in processes as diverse as synaptic transmission and hormone secretion. Recent studies have revealed that cells have proteins that can sense directly the shape of a membrane. These membrane curvature sensors bind specifically to highly curved membranes, such as those of transport ves icles, and play important roles in organizing membrane trafficking processes. Our group, in collaboration with Bruno Antonny's laboratory, has recently demonstrated that two different curvature sensors, which form amphipathic helices on membranes, have specific chemistries that allow them to detect the different lipid compositions of their target vesicles directly. Intriguingly, these two amphipathic curvature sensors represent the two extremes of amphipathic helical structure, and are adapted to the two major lipid environments of the cell, nuclear envelope-ER-early Golgi and late Golgi-endosome-PM. To date, only a few membrane curvature sensors have been characterized, but bioinformatics studies indicate that many more of these biosensors exist in cells. The doctoral project will consist of cell biological studies to uncover the specific roles of these novel membrane curvature sensors in intracellular membrane trafficking pathways, and their biochemical and biophysical c haracterization in collaboration with Bruno Antonny's group.

Interdisciplinarity of the project

This project is a collaboration between two groups, the Jackson laboratory at the Institut Jacques Monod in Paris and the Antonny laboratory at the Institut de Pharmacologie Moléculaire et Cellulaire/Université de Nice in Sophia Antipolis. C. Jackson's group has expertise in cell biological approaches to studying membrane trafficking, using both yeast and mammalian cells as model systems. B. Antonny is an expert in biochemistry and biophysical approaches to studying membrane-protein interactions. The graduate school that the hosting lab (Jackson) is affiliated with - Genes, Genomes, Cellules - is principally concerned with cell biological and developmental approaches. The interdisciplinarity of this project, including both cell-based and biophysical methodologies, makes it ideally suited to the FdV program.