Date : 17/05/2011

Internship proposal for : Master 1 or Master 2

Laboratory
Membrane dynamics and Intracellular Trafficking UMR 7592
Institut Jacques Monod, CNRS & Université Paris Diderot Paris 7
Bât.Buffon - 15 rue Hélène Brion 75205 Paris Cedex 13
Website : http://www.ijm.fr/en/ijm/research/research-groups/membrane-dynamics/
Main discipline : Cell Biology
Lab director : Cathy Jackson

Mentor
Cathy Jackson
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : 01 69 82 34 91

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

Tools and methodologies
1.: Live cell imaging/FRAP microscopy
2.: Cell culture and immunofluorescence microscopy
3.: Molecular design and purification of bioprobes

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 characterization in collaboration with Bruno Antonny's group.