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PhD (M/W): interfacial biochemistry of perilipins, lipases and CIDE proteins

This offer is available in the following languages:
Français - Anglais

Date Limite Candidature : mercredi 14 décembre 2022

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General information

Reference : UMR7275-BRUANT-003
Workplace : VALBONNE
Date of publication : Wednesday, November 23, 2022
Scientific Responsible name : Bruno Antonny and Joëlle Bigay
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 2 January 2023
Proportion of work : Full time
Remuneration : 2135 euros (gross) and 1715 euros (net) per month

Description of the thesis topic

Lipid droplets are atypical intracellular organelles. Formed by a core of neutral lipids, cholesterol esters and triglycerides, they allow the storage of a large amount of metabolic energy in a minimal volume. The stored fatty acids and sterols can then be mobilized to provide energy or serve as precursors for more complex lipids, including the phospholipids of biological membranes. Almost all cells have lipid droplets, but some tissues have particularly developed this organelle; notably white adipocytes where most of the volume is occupied by a single droplet of several tens of micrometers in diameter.
The biochemistry at the surface of lipid droplets is not well known because this interface is without equivalent in the cell. In contrast to organelles surrounded by a lipid bilayer, the surface of lipid droplets is a monolayer made of phospholipids and proteins whose composition, structure, and temporal variations during the phases of lipogenesis and lipolysis remain to be characterized at the molecular scale. This is also an issue in health because the dysfunction of droplets is at the heart of many diseases. For example, the correlation between adipocyte size and cardiovascular risks is not understood.
The objective of the thesis is to understand the molecular changes at the surface of lipid droplets during lipolysis and fusion reactions. The student will explore how proteins and phospholipids are arranged at the surface of droplets, in particular perilipins which form a family of long amphipathic proteins specially adapted to cover the surface of droplets. Are the perilipins sitting on a phospholipid monolayer or directly in contact with the triglycerides? What are the mechanisms that explain the covering of droplets by different perilipins in the same cell? What are the interaction modes and conformational changes that allow perilipins to control lipases (HSL, ATGL) and fusion proteins (CIDE)?
The student (M/W) will use biochemical reconstitution and cell biology approaches as well as biophysical measurements. He/she should have an excellent background in biochemistry.

Work Context

The candidate (M/W) will join the Antonny team - Dynamics of membranes and protein coats - within the Institute of Molecular and Cellular Pharmacology. This Institute includes more than 200 people divided in 20 teams. The Antonny team includes 4 researchers, one assistant professor, one post-doc researcher, three PhD students and four engineers.

Constraints and risks


Additional Information

This thesis project is funded by the ERC synergy program “SPHERES” in collaboration with Dominique Langin (University of Toulouse), Mickael Ryden (Karolinska Institute, Sweden) and Alenka Copic (CNRS, Montpellier). The supervisors are Bruno Antonny (CNRS research director, HDR) and Joëlle Bigay (CNRS research fellow, HDR).

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