Students

Anneline Moret, Ph.D Candidate Eutopia Royle Lab/ERRMECe Lab ROCK-I Project (Supervision Ambroise Lambert/Franck Carreiras/Steve Royle)

Research Motto: Eternal sunshine of the spotless integrins! The return

Anneline Moret is a EUTOPIA co-tutelle doctoral student who’s working on the modulation of integrins ⍺5β1 on the surface of ovarian cancer cells to study its effects on the cancer microenvironment.

In many cancers, integrins are overexpressed leading to abnormal cell behaviours. The 24 different integrin heterodimers are crucial in cell signalling; they act as a bidirectional centre of communication between cell microenvironment and intracellular signalling. In ovarian cancer, a5b1 and avb3 integrins both bind to fibronectin and participate to cancer dissemination. Interaction with extracellular matrix (ECM) is crucial for cancer spreading from spheroid formation to implantation. But how to study these interactions in an acute manner? A rapid modulation of these interactions, by removing a5b1 integrins for the plasma membrane, has been made possible by a technique called: “Hot-wiring”. Removal of integrins could be triggered within minutes by chemically inducing endocytosis through the canonical clathrin pathway. Her work will focus on: (1) extending this toolbox from transient transfection to an CRISPR-edited cell line where endogenous integrin a5 is tagged with mCherry-FRB at the C-terminus and viral transduction to express the hooks FKBP-AP2B1-GFP or GFP-FKBP, (2) apply it to also remove avb3 integrins, (3) and finally use these cell lines to study effect of reducing cell interactions during cell adhesion to the ECM, spheroid formation and epithelial-mesenchymal transitions.

Marion Theuret, Ph.D Candidate (MesoCell Project, Supervision: Franck Carreiras, Sabrina Kellouche, Ambroise Lambert)

Research Motto: No player is greater than the game itself (Rollerball 1975)

Ovarian cancer dissemination spheroid model morphodynamics in co-culture models. Cells interact with the surrounding extracellular matrix. Interactions induce signalling and regulation of cell behaviour, which contribute to cell heterogeneity. Biochemical and biophysical inputs from microenvironment of cells have a pivotal role in development, physiological processes and pathologies, like tissue regeneration, ageing and tumour development. They also modulate drug response and materials bio-integration. The cell matrix interactions are “universal”, but happen at different time, mechanical and spatial scales: from single cell receptors binding to extra-cellular matrix molecules at nanometer scale with forces of piconewtons in milliseconds, at the tissue millimeter scale with forces up to newtons in days. They are illustrated with physio pathological processes like: fast even instantaneous haemostasis for in

wound healing or slower, chronical processes like aging. Bridging these scales is a major challenge to propose unifying model of cell

heterogeneity and to identify and target relevant cell microenvironment interactions for diagnostic markers, well-being and therapeutic avenues, or tissue engineering strategies. We recently developed flash multiscale tuning of cell-matrix interactions

(Warwick University/ CY Cergy Paris), from molecules to groups of cells within minutes to span across all the scales. We obtained a proof of concept in ovarian cancer and show promising results that tune protein trafficking inducing single cell control of microenvironment interactions. We can also prevent formation of tumour spreading spheroids, leading to a potential therapeutic strategy.

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