About
I am interested in the molecular mechanisms that regulate lipid organization and transport within the cell, particularly at membrane contact sites. These structures correspond to areas of close proximity between organelles, notably between the endoplasmic reticulum and other compartments, allowing direct exchange of lipids and signals without membrane fusion. Contact sites play a crucial role in lipid homeostasis, cell signaling, and organelle function, and their dysfunction is implicated in numerous pathologies. Furthermore, many RNA viruses, particularly... Orthoflavivirus (e.g., dengue virus and Zika virus), hijack these membrane structures and the lipid metabolism of the host cell in order to promote their replication.
Thus, our research lies at the interface of cell biology, membrane biophysics, and human pathophysiology. We seek to understand how the spatial organization of membranes and lipid transport contribute to normal cell function and how their dysregulation contributes to human diseases.
Our current projects aim to:
- Establishing a new link between membrane contact sites, lipid transport and production of pulmonary surfactant.
- Define the mechanistic and structural bases of major components regulating the’cellular cholesterol homeostasis.
- Better understanding the Zika virus dependence on host lipid pathways and to identify vulnerabilities that can be exploited for therapeutic purposes.
General audience summary
The cells in our body are made up of specialized compartments called organelles, each of which performs specific functions. To function properly, these organelles must exchange essential molecules, including lipids, which are major components of cell membranes and play a key role in energy production, signaling, and cell protection.
Contrary to previous assumptions, these exchanges do not rely solely on vesicles, but also on areas of direct contact between organelles. These membrane contact sites allow for rapid and controlled lipid transfer and contribute to the overall organization of the cell.
I study the proteins that control these exchanges and their role in health and disease. These lipid transport mechanisms are essential in vital functions such as pulmonary respiration and cholesterol regulation, and they can also be exploited by certain pathogenic viruses to multiply.
By understanding these fundamental processes, our research aims to identify new therapeutic targets, and ultimately, this work could contribute to the development of new strategies to treat important human diseases.
Main scientific collaborations
- Daniel Lévy (Curie Institute, Paris)
- Fanny Roussi (Curie Institute, Orsay)
- Abdou Rachid Thiam (ENS Physics, Paris)
- Matias Simons (UKHD Heidelberg)
- Cazikano Consortium (PIMIT, La Réunion; Inst. Pasteur, Paris/Lille; IRSET, Rennes; ICSN, Gif-sur-Yv.)
Recent discoveries
Our work has identified fundamental mechanisms governing the intracellular transport of cholesterol and the structural organization of membrane contact sites between the endoplasmic reticulum and the network trans-Golgien. We have notably demonstrated that the OSBP protein acts as a lipid transporter capable of’exchange cholesterol for another lipid, phosphoinositide PI(4)P, thus ensuring massive and directional transport of cholesterol between organelles.
We have highlighted that VAPA, the universal transmembrane receptor of the endoplasmic reticulum and partner of OSBP, has flexible regions that play a vital role in the organization and dynamics of membrane contact sites, by enabling structural adaptation to the physical constraints of membranes. These results revealed how the structural properties of proteins contribute to the stability and plasticity of these membrane interfaces.
Some RNA viruses belonging to the family of Flaviviridae, including those of the genre Orthoflavivirus, notably the Zika virus or the dengue virus, utilize the host's protein machinery, including OSBP, to remodel intracellular organelles to promote their replication. In the context of these viral infections, we have identified a novel molecule capable of specifically inhibiting OSBP without cellular toxicity, opening significant avenues for the development of therapeutic strategies targeting lipid transport.
Events
«Back to the roots, molecular mechanism of nonselective autophagy«
«OSBP and VAP twins in motion: dynamics, partners, and structural organization at membrane contact sites» Directors of […]
Projects
This project aims to understand how membrane contact sites contribute to the production of pulmonary surfactant, a lipid-rich substance essential […]
Many viruses exploit host cell membranes and lipid metabolism to ensure their replication. The Zika virus, in particular, hijacks membranes […]
Cholesterol is an essential component of cell membranes and a precursor to many biological molecules. Its concentration must be strictly […]