Mechanobiology of Host-Microbe interactions
Presentation
The team Mechanobiology of Host-Microbe Interactions (MoHMI) is interested in understanding how physical forces can impact infections at the epithelial barriers. Our laboratory is particularly interested in Shigellosis, a diarrheal disease related to infection caused by Shigella. These bacteria penetrate and take advantage of the internal molecular machinery of the host cell to propel themselves and spread rapidly into neighboring cells of the intestinal epithelium, leading to tissue destruction, inflammation and the development of severe diarrhea. Recently, we have discovered that the infection capacity of Shigella is very sensitive to mechanical forces including peristalsis-related stretching forces. We are now exploring the strategies used by Shigella to manipulate the physical force-sensitive machinery of the host cell and promote its propagation within the tissue. To do so, we are developing new tools based on microfabrication and microfluidics, including the creation of advanced micro physiological systems also known as organ-on-a-chip. Our research spans several fields, including cell biology, genetics, microbiology and bioengineering.
Highlights
- The team Mechanobiology of Host-Microbe Interactions newly installed in 2022 in the unit U1019/UMR 9017/Univ Lille/CHR Lille is currently supported by a CNRS-INSERM ATIP-Avenir funding and also by funding from the Hauts-de-France Region and European Metropole of Lille (MEL). These financial supports allow us to advance our fundamental research theme aiming to better understand the role of mechanical forces in bacterial infections but also to develop an innovative applied research by designing new technologies such as organ-on-a-chip. These new cell culture systems are part of a 3R approach and are considered as a major hope in many biomedical applications such as pharmacology, preclinical toxicology and personalized medicine.
Transversal projects
Respiratory infections and tubeculosis
In collaboration with Priscille Brodin’s team (IP Lille) and Roland Brosch’s team (IP Paris), a lung-on-a-chip system is being developed to study respiratory infections related to Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. This project is funded by the network of Institut Pasteur of Paris, Pasteur Network- PTR-430-21.
Members
Alexandre GRASSART
PhD, Team Head
ORCID number : 0000-0002-9656-4331
PhD, Post-doc
Laurine DE RICKER
Research assistant
Publications
Grassart A, Malardé V, Gobaa S, Sartori-Rupp A, Kerns J, Karalis K, Marteyn B, Sansonetti P, Sauvonnet N
Bioengineered human organ-on-Chip reveals intestinal microenvironment and mechanical forces impacting Shigella infection.
Cell Host & Microbe 2019 Sep 11;26(3):435-444 #Co-corresponding authors
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.
Shigella flexneri induces a global blockage in host cell intracellular transport leading to cell and tissue disorganization.
PNAS 2019 Jul 2;116(27):13582-13591.
Bertot L, Grassart A, Lagache T, Nardi G, Basquin C, Olivo-Marin JC, Sauvonnet N.
Quantitative imaging and statistical analysis of the dynamics of clathrin-dependent and -independent endocytosis reveal a differential role of endophilinA2 in dynamin2 recruitment.
Cell reports 2018. Feb 6;(22):1574-1588
Pinilla-Macua I, Grassart A, Duvvuri U, Watkins SC, Sorkin A.
EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo.
eLife 2017 Dec 21;6
Grassart A, Cheng AT, Hong SH, Zhang F, Zenzer N, Feng Y, Briner DM, Davis GD, Malkov D, Drubin DG
Actin and dynamin2 dynamics and interplay during clathrin mediated endocytosis.
J Cell Biol Jun 205 (5):721-735
Keywords
Allergy ; Asthma ; Acute respiratory ; Distress syndrome ; Endothelial cells ; Lymphoid cells immunity