Mechanobiology of Host-Microbe Interactions (MoHMI)
Alexandre GRASSART, a French national, studied Cell Biology at the Institut Pasteur in the laboratory of Professor Alice Dautry-Varsat and obtained a PhD from the University Paris-Saclay in 2010. He completed a post-doctoral fellowship at UC Berkeley (USA) in the laboratory of Professor David Drubin during which he acquired a recognized expertise in the field of Cell Biology and Bioengineering. He then joined back the Institut Pasteur in the team of Dr. Nathalie Sauvonnet in the laboratory of Professor Philippe Sansonetti in 2014 where he studied intestinal infections caused by the pathogen Shigella. In 2020, he joined the Chinese Academy of Sciences (CAS) as Professor and established the Bioengineering and Microbiology Laboratory at the Institut Pasteur of Shanghai-CAS. Since 2022, he joined the CNRS UMR9017, INSERM U1019 and Institut Pasteur of Lille as a laureate of the CNRS INSERM ATIP/AVENIR Young Researcher Program and obtained a tenure track position at INSERM the same year. His team is now studying the role of mechanical forces in bacterial infections and is developing advanced microfluidic technologies such as "organ-on-a-chip" systems dedicated to the study of host-microbe interactions.
The "Mechano-biology of Host-Microbe Interactions" team aims to understand how tissue microarchitecture and mechanical forces impact pathogen interactions at the mucosal barrier interface. Our main effort focuses on intestinal infections and we are currently using Shigella as a pathogen model. These bacteria penetrate and exploit the internal molecular machinery of the host cell to propel themselves and spread rapidly to neighboring cells of the epithelium. This infection leads to a major inflammation of the colon followed by severe diarrhea, which can be fatal in particular for children under 5 years old. Recently, we have discovered that Shigella infectivity is very sensitive to mechanical forces related to peristalsis. We now aim to identify the strategies used by Shigella to manipulate the mechano-sensitive machinery of the host cell that promotes the internal propagation of Shigella from one epithelial cell to another. To this end, we are developing new cell culture systems known as organs-on-a-chip, micro-physiological systems based on microfabrication and microfluidics. Our research spans several fields, including cell biology, genetics, microbiology and bioengineering.
1.Mottet Guillaume*, Grassart Alexandre*#, Barthelemy Philippe, Devillier Philippe, Antignac Corinne, Arrabal Samuel, Bourdin Arnaud, Descroix Stéphanie, De Vos John, Doutriaux Agathe, Fabrega Quentin, Galaud Anne, Graff-Dubois Stéphanie, Houeto Paul, Illiano Stéphane, Legallais Cécile, Louin Gaelle, Maisonneuve Benoit, Piwnica David, Quemeneur Pierre, Salentey Valérie, Salomon Valérie, Rozenberg Julian, Sotiropoulos Athanassia, Tomasi Raphael, Vergnolle Nathalie. (submitted) Organoids, Organs on chip, CIVM : Definition, applications, validation and ethics. *These authors contributed equally to this work , # Corresponding authors
2.Boquet-Pujadas A, Feaugas T*, Petracchini A*, GrassartA, Mary H, Manich M, Gobaa S, Olivo-Marin J-C, Sauvonnet N, Labruyère E. (2022). Oct 21;8(42). (Science Advances).4D live imaging and rheology of organs-on-chips reveal how gut-like peristalsis facilitates tissue infection by Shigella flexneri and Entamoeba histolytica. *These authors contributed equally to this work
3. Salavessa L, Malardé V, Lagache T, Grassart A, Canette A, Trichet L, Sauvonnet N (2021) Sep 14;118(37) (PNAS). Cytokine receptor cluster size impacts its endocytosis and signaling.
4.Grassart A#, Valérie Malardé, Gobaa S, Anna Sartori-Rupp, Jordan Kerns, Katia Karalis, Benoit Marteyn, Sansonetti P and Sauvonnet N#. (2019) Sep 11;26(3):435-444 (Cell Host & Microbe). Bioengineered human organ-on-Chip reveals intestinal microenvironment and mechanical forces impacting Shigella infection. # Corresponding authors
5.Ferrari M, Malardé V, Grassart A, Salavessa L, Nigro G, Decorps-Leclere S, Masson V, Arras G, Loew D, Rhode J, Sansonetti Pj, Sauvonnet N. (2019) Jul 2;116(27):13582-13591. PNAS. Shigella flexneri induces a global blockage in host cell intracellular transport leading to cell and tissue disorganization.
