The Lavieu Lab
In order to help strengthen the international scientific positioning and attractiveness of Université de Paris, an action “IdEX Chairs” has been launched. This call for proposals aims to promote the hosting of researchers from outside the institution whose profile corresponds to internationally renowned seniors or juniors with very high potential.
Already 7 laureates in the last two years, including Grégory Lavieu who joined Université de Paris on the research site of the Saint-Germain-des-Prés campus to set up a team dedicated to intra- and extracellular membrane transport and thus strengthen the Cell Biology cluster.
Electron micrograph showing extracellullar vesicles.
Gregory Lavieu, PhD (PI). G. Lavieu is a cell biologist/biochemist expert in membrane trafficking. G. Lavieu is currently an INSERM permanent investigator, and “Chaire IdEX” in Université de Paris, within the UMR7057 Research Unit.
Previously, G. Lavieu identified and characterized a new mode of intra-Golgi transport, termed Rim progression, dedicated to oversized proteins that are too large to fit into classical transport vesicles.
More recently, G. Lavieu and his research group aim at characterizing the intercellular transport mediated by extracellular vesicles (exosomes), at both cellular and molecular levels. Their goal is to identify the core machinery controlling this process.
Extracellular Vesicles (EVs), including Exosomes, are now recognized as vectors of intercellular communication capable of transferring nucleotides, lipids, and proteins from donor to acceptor cells. EV-mediated communication has been associated with many physiological and pathophysiological functions, including cancer, immune responses, cardiovascular diseases, lipid homeostasis, tissues regeneration and stem cell-based therapy.
EVs are being recognized as vectors of major importance for physiology in general, and appears as promising candidates for translational applications such as targeted therapeutics delivery.
*However, the mechanisms responsible for EV delivery within the acceptor cells remain unknown at both the cellular and the molecular levels. How do vesicles enter cells? Is it receptor-dependent? How do vesicles deliver their contents within the cytosol of the acceptor cells? Does it require membrane fusion? If yes, what is the nature of the target membrane and the fusion machinery? Those basic questions are not yet answered.
This is not satisfying, especially considering how much we know about the cellular and molecular mechanisms that regulate the delivery of viruses or the transport of intracellular vesicles, which both share several physico-chemical properties with EVs.
It is therefore of high priority to close these gaps, especially when considering the high translational impact of EVs.
We developed cell-free and cell-based assays to accurately assess in a qualitative and quantitative manner the EV delivery process, especially the EV content release. Our results suggest that EV content delivery occurs within the endo-lysosomal compartment, through a process that is pH- and protein-dependent and that seems to involve membrane fusion. We are now aiming at identifying the core machinery that controls this process, to later engineer EV-mimetics designed for targeted therapeutics delivery.
Diagram representing the different possible routes used by the vesicles to release their contents into the receiving vesicles.
Selected relevant publications:
- Bonsergent E, Lavieu G. Content release of extracellular vesicles in a cell-free extract. FEBS Lett. 2019 doi: 10.1002/1873-3468.13472.
- Murphy DE, de Jong OG, Brouwer M, Wood MJ, Lavieu G, Schiffelers RM, Vader P. Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking. Exp Mol Med. 2019 doi: 10.1038/s12276-019-0223-5.
- Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019 doi: 10.1038/s41556-018-0250-9.
- Mocciaro A, Roth TL, Bennett HM, Soumillon M, Shah A, Hiatt J, Chapman K, Marson A, Lavieu G. Light-activated cell identification and sorting (LACIS) for selection of edited clones on a nanofluidic device. Commun Biol. 2018. doi: 10.1038/s42003-018-0034-6.
- Spotlight on early-career researchers: an interview with Gregory Lavieu. Commun Biol. 2018. doi: 10.1038/s42003-018-0144-1.
Motivated individuals interested in this work and wishing to do a postdoctoral fellowship or a thesis are encouraged to contact Dr. Lavieu.
Please include your c.v. and a brief research summary, and have three letters of recommendation emailed to Dr. Lavieu.
Emeline Bonsergent (PhD Student). Emeline is developing cell-free and cell-based assays to assess EV-delivery and then test the impact of new candidate proteins involved in the pathway.
Sheryl Bui (MD/PhD Student). Sheryl is investigating if viral-derived proteins are involved in EV-delivery and then aims at developing EV-mimetics for targeted therapeutics delivery.
Julia Dancourt, PhD (Senior Scientist). Julia is performing genome-wide screenings to identify key actors of EV-delivery.
Zahra Al Amir Dache, PhD (Post-doctoral Researcher). Zahra is investigating EV-mediated communication between Legionella pneumophila and human target cells, and aims at identifying if the EV-delivery core machinery is conserved through evolution.
Scientific Partners (within UMR7057)
Stéphanie Mangenot, PhD (Professor, Université de Paris). We are studying fusion between EVs and target membranes using in vitro systems.
Amanda Brun, PhD (CNRS, CRCN) and Florence Gazeau, PhD (CNRS, DR). Applying turbulence on donor cells massively increases EV production. We are investigating the delivery capacity of those turbulence-induced EVs.
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