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Optogenetic interrogation of engineered microtissues

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Mechanical signals, such as forces or stiffness, are crucial to many biological processes over a range of length scales. This project aims at studying how these signals are spatially propagated and temporally stored in biological tissues. To this end, this project combines cutting edge technologies in tissue engineering with recent advances in optogenetics. On one hand, microfabrication techniques allow for measuring the forces generated by 3D multicellular tissues. On the other hand, the use of photosensitive-ArhGEF11 fibroblasts allows for a precise spatio-temporal control of cell forces from the inside, as ArhGEF11 is a major regulator of cellular contractility. This challenging internship will provide a highly interdisciplinary training, as the student will learn praised skills in different aspects of bioengineering, from materials science to fundamental biology and biophysics

A major focus of this project consists in investigating the influence of several parameters (cell density, extracellular matrix composition, energy of stimulation) that might impact the response of a model tissue to local mechanical perturbation. Our approach involves the in situ formation of 3D microtissues by culturing photo-sensitive fibroblasts embedded within a tunable biopolymeric matrix in a microfabricated platform. Using this platform, we are uniquely able to measure both fine-scale cytoskeletal and extracellular architecture, as well as cell-generated forces. The local perturbation will be triggered by optogenetics, i.e. light stimulation of a protein regulating cell contractility .The platforms will be microfabricated by soft lithography. The formation and tension of the microtissues will be assessed by time-lapse microscopy. The characterization of the tissue response to stimulation will be done by using a digital micro- mirror device (DMD) to control the shape of the stimulating light.

Location :
The candidate will work at the Laboratory for Interdisciplinary Physics (LIPhy), in the MOTIV team (Materials, Optics and Instrumental Techniques for the Life Sciences).
LIPhy : https://www-liphy.ujf-grenoble.fr/

Profile & requested skills :

5th year engineering school student and / or Master student whose training focuses primarily on biophysics, tissue engineering, biology and biomaterials. We are looking for highly motivated scientists with an aptitude for teamwork and good
ommunication skills in oral and written English.

Subject could be continued with a PhD thesis

Allowance :
Internship allowance will be provided ( 500€/month)

CONTACT :
Please send a CV + a cover letter (including names/contact email of 2 referees) + he record of your grades of the 2 past academic years (2015/2016 & 2016/2017) to
homas Boudou (thomas.boudou@univ-grenoble-alpes.fr) and Martial Balland (martial.balland@univ-grenoble-alpes.fr)