Description of the thesis topic

Organelles are distinct compartments within cells, each characterized by a specific biophysical and biological identity shaped by their lipid and protein makeup. The endoplasmic reticulum (ER) is the primary location for protein and lipid synthesis, interacting with all other organelles to regulate cellular functions and metabolism. This regulation heavily depends on the ER's dynamic connections with other organelles, especially lipid droplets (which function as energy storage) and mitochondria, which are responsible for both the anabolic and catabolic processes of lipids. Additionally, various organelles engage in contact and material exchange amongst themselves. In conditions like Alzheimer's disease or liver steatosis, these connections and lipid exchanges become disrupted, making it essential to comprehend their formation for fundamental research and health.

Although the ER, LD, and mitochondria are structurally distinct, they are central to cellular lipid metabolism. Their biophysical properties dynamically change in response to metabolic cues, yet they remain uncharacterized, and their influence on organelle function is still poorly understood.

In this thesis, we aim to recreate ex-vivo organelle interactions, examine how lipid composition influences the biophysical traits of the organelles (such as tension, elasticity, and rigidity), facilitate lipid exchange among organelles, and de novo reconstruct lipid synthesis and organelle formation from these reconstituted organelles. This can be achieved using extracts sourced from both healthy and diseased cells.
Our work will be led by a highly interdisciplinary team that has already developed the necessary tools to conduct such a project. We seek a highly dynamic and motivated student willing to embark on a multidisciplinary, biophysics-driven project.

Work Context

This PhD project will take place at the Laboratoire de Physique de l'École Normale Supérieure (LPENS), located at 24 rue Lhomond, 75005 Paris, within the Physics Department of ENS-PSL. LPENS is a leading fundamental research laboratory operating at the interface of physics, biology, mathematics, and cognitive sciences.

The project will be carried out in a highly interdisciplinary research environment, bringing together expertise in membrane biophysics, cell biology, advanced imaging, and quantitative modeling. The PhD candidate will benefit from access to cutting-edge technological platforms (including high-resolution microscopy, lipid mass spectrometry, and functional genomics), as well as from a multidisciplinary mentoring team that fosters interaction between physicists, biologists, and chemists.

Constraints and risks

Biology