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Biomaterials to study the early step of Sars-Cov 2 virus/host cell interactions

Published on 18 November 2020
Context
The Sars-Cov 2 virus is a major threat for the population and different strategies are currently being investigated to develop innovative treatments, including vaccines or new drugs. The entry of the virus is known to be mediated by the viral spike protein, which contains a RBD domain that interacts with ACE2 receptor in the host cell. However, to date, there is a poor understanding of the molecular basis of cell signaling triggered by Spike S protein/ACE2 receptor interactions. This signaling is likely to involve the renin/angiotensin system [1] and its downstream effectors. Our team has developed biomaterials, namely bioactive surface coatings presenting proteins at the basolateral side of cells in a controlled manner [2]. These coatings can be deposited in microplates for high content studies of cellular processes [3]. They will be developed here to study the early steps of virus/host cell interactions.

Project description
The objective of this project is to mimic the early steps of Sars-Cov-2 host cell invasion by initiating ACE2 cell signaling in a “virus free” approach (Figure above). This will be achieved using a biomaterial presenting the spike protein or RBD fragment, named hereafter Bioactive-Spike. We will use physiologically relevant cell cultures of three major infected organs (kidney, intestine, lung) and will assess the activity of the ACE2 receptor using different types of biological assays and cytoskeleton imaging. We further aim to identify the ACE2 co-receptors in a cell-specific context using selected inhibitors. To reach this objective, the candidate will learn to use a liquid handling robot to prepare the biomaterials, cell culture, immuno-fluorescence staining, high content microscopy and biological assays.

Student profile
We are looking for an Engineer/M2 student interested in working in a multidisciplinary environment. The student will be part of dynamic and international research teams working with several collaborators and organizing weekly seminars. The working language is english but the majority of team members are fluent in French.

Related Publications
[1] B.A. Wevers, L. van der Hoek, Renin-angiotensin system in human coronavirus pathogenesis, Future virology 5(2) (2010) 145- 161. 
[2] F. Gilde, R. Guillot, I. Pignot-Paintrand, T. Okada, V. Fitzpatrick, T. Boudou, C. Albiges-Rizo, C. Picart., Cellular internalization of matrix-bound BMP-2 and associated endocytosis pathways, Acta Biomaterialia 46 (2016) 55-67. 
[3] P. Machillot, Quintal, C., Dalonneau, F., Hermant, L., Monnot, P., Matthews, K., Fitzpatrick, V., Liu, J., Pignot-Paintrand, I., Picart, C, Automated buildup of biomimetic films in cell culture microplates for high throughput screening of cellular behaviors Advanced Materials e1801097 (2018).

Supervisors
BRM (Catherine Picart, Paul Machillot),
IMAC (Odile Filhol Cochet, Nadia Cherradi)

Laboratory : BRM & IMAC teams 

Contact for your application
Please send your CV, a motivation letter as well as 2 names of referees + the transcript of your grades for the two last years of study (2018/2019 and 2019/2020) to Catherine Picart

Web-page 

Superviseur :
Nadia Cherradi