Description du sujet de thèse

This PhD project, funded by the CNRS 80 Prime program, is part of a collaboration between two research teams with complementary expertise in cell biology and membrane biophysics. The objective is to elucidate the structural, molecular, and biophysical mechanisms regulating the formation, growth, and renewal of lipid droplets (LDs) at endoplasmic reticulum (ER) membranes associated with mitochondria, known as MAMs (Mitochondria-Associated Membranes).
LDs are dynamic organelles essential for lipid storage and energy homeostasis. Their dysfunction is implicated in metabolic diseases such as obesity, diabetes, lipodystrophies, and neurodegenerative disorders. MAMs are specialized contact sites between the ER and mitochondria and serve as key platforms for lipid exchange between these organelles.
The team recently identified a novel tripartite junction between mitochondria, the ER, and LDs (MAM-LD) with unique morphological and functional characteristics. The project aims to characterize the architecture and molecular components of these junctions. A particular focus will be on lipid transporters localized at MAMs, which are likely to regulate local phospholipid and sterol fluxes and influence lipid fate (storage vs. metabolic conversion).
The PhD candidate will adopt an interdisciplinary approach combining various techniques including advanced cell imaging (confocal and super-resolution microscopy, transmission electron microscopy, and 3D FIB-SEM), subcellular fractionation, biochemistry, membrane biophysics, and in vitro and ex vivo lipid transfer assays.
Project Objectives:
1. Characterize the morphology and molecular composition of MAM-LD junctions in various mammalian cell types and metabolic contexts, including pathological conditions (e.g., hepatic steatosis, lipodystrophies).
2. Investigate the role of metabolic and lipid transport proteins in regulating LD and mitochondrial dynamics.
3. Explore how lipid exchanges at MAMs are coordinated with other intracellular contact sites, such as ER–plasma membrane junctions.
The expected outcomes will provide a better understanding of how MAMs orchestrate intracellular lipid fluxes and their involvement in diseases such as obesity, diabetes, neurodegeneration, and certain cancers.

Contexte de travail

The project will take place at the I2BC (Institute for Integrative Biology of the Cell), a joint research unit of the CNRS, CEA, and Université Paris-Saclay, comprising around 600 researchers across five scientific departments. The institute hosts 17 high-level technological platforms and shared support services.
The PhD candidate will join the “Lipid Trafficking and Membrane Contact Sites” team, led by Francesca Giordano, within the Cell Biology Department, located on the CNRS campus in Gif-sur-Yvette (Île-de-France). The team, currently composed of of six members (1 Inserm Research Director, 1 postdoc, 2 research engineers, 2 PhD students) will welcome three new members in September 2025 (1 postdoctoral fellow, 1 visiting associate professor, and 1 visiting PhD student). The team has recognized expertise in membrane dynamics, electron microscopy, and the study of inter-organelle contact sites.
The PhD student will be directly supervised by the team leader and a postdoc with strong expertise in high-resolution imaging and lipid analysis, as well as supported technically by an engineer specialized in electron microscopy. The student will benefit from a stimulating scientific environment and privileged access to state-of-the-art technological platforms. A major advantage is the immediate proximity to the Imagerie-Gif platform, which houses cutting-edge equipment for fluorescence and electron microscopy, and to the proteomics platform.
The project will be conducted in close collaboration with Dr. Abdou Rachid Thiam's team (ENS Paris, Physics Laboratory), specialists in lipid droplet biophysics and membrane reconstitution ex vivo. As part of the 80 Prime PhD program, the student will have the opportunity to engage in regular collaborative work and receive training with this team. The project will also benefit from ongoing collaborations of F. Giordano's team—at the Paris-Saclay campus, as well as at national and international levels—with experts in lipid metabolism and adipocyte physiology.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

This position falls within a sector subject to the Protection of Scientific and Technical Potential (PPST). In accordance with regulations, your appointment must be authorized by the competent authority of the French Ministry of Higher Education and Research (MESR).