The Laboratory of Membrane Protein and Membrane Systems works at deciphering the mechanism of membrane-related processes, with a specific emphasis on the molecular mechanism of active transport across biological membranes, as well as the study of protein-protein and protein-lipid interactions and significance. We use a combination of complementary experimental and in silico approaches: biochemistry, spectroscopies, molecular dynamics simulations and structural methods.
Description
The cells from our body as well as intracellular organelles are surrounded by a thin sheet called the membrane, which is primarily made of lipids and proteins. Membranes are much more than merely a barrier that insulates the outside medium from the inside of the cell. Membranes coordinate a number of cell signaling events, e.g. through the recruitment of peripheral proteins like small G proteins. Besides, chief amongst the cell membranes constituents are integral membrane proteins, which act as biological gatekeepers, controlling the flow of biomolecules through transporters and transmitting signals through receptors. As such, integral membrane proteins are involved in a host of different functions, ranging from cell signaling, membrane trafficking, ion/lipid transport, cell detoxication, cell energization, to the generation of membrane potential. This is exemplified by the fact that 30% of a large number of genomes encodes membrane proteins and that about 50% of currently used drugs target membrane proteins. Membrane proteins have also important roles in the pharmacokinetics (tissue distribution, metabolism and clearance), safety and efficacy profile of many pharmaceutical drugs, and in the drug-resistant mechanisms operating in many pathogens.
In sum, damages to membranes can grossly alter most processes within the cell. Furthermore, although the role of lipids has long been underestimated, they now take center stage as we begin to understand their role in membrane trafficking, signaling, nanodomain organization, energy storage, or the regulation of membrane protein activity.
In our group, we aim to decipher the mechanism by which membrane proteins catalyze their function, at a molecular level, with a specific emphasis in the interplay between lipids and membrane proteins, and in the role of membrane proteins in the dynamic organization of membrane lipids. Four main research axis revolve around and centre on this general theme:
Molecular mechanism of fLippase-catalyzed transbilayer lipid transport (axis 1)
Investigation of caveolin-1 structure and lipid-protein interactions in caveolae (axis 2)
Structure, function, and regulation of disease-related membrane transport proteins (axis 3)
To that purpose, we use a combination of complementary experimental and
in silico approaches: biochemistry, spectroscopy, molecular dynamics simulations and structural methods. As part of the French Infrastructure for Integrated Structural Biology (
FRISBI), our laboratory hosts the yeast expression technical platform MPEX (
Membrane
Protein
EXpression) and therefore state-of-the-art equipment for membrane protein expression and purification.
Human resources
Azouaoui Hassina, PhD Student
Barbot Thomas, PhD Student
Beswick Véronica, assistant Professor
Champeil Philippe, Researcher
Garrigos Manuel, Researcher
Haraux Francis, Researcher
Jamin Nadège, Researcher
Jaxel Christine, Researcher
Le Maire Marc, Professor
Lemaire Claire, Researcher
Lenoir Guillaume, assistant Professor
Montigny Cédric, Engineer
Orlowski Stéphane, Researcher
Perrot Nahuel, PhD Student
Roux Michel, Researcher
Vázquez-Ibar José-Luis, Researcher