Optogenetics to study interactions between normal and transformed cells2013 - I. Bonnet (team Silberzan/Buguin, UMR168)
In living organisms, cells continuously interact and compete for resources and space. These competitive interactions that lead to the elimination of non-optimal cells are crucial to maintain tissue integrity and function. Competitive cell interactions may also play a role in cancer. It has indeed been proposed that precancerous cells could act as super-competitors killing surrounding cells to make more space for themselves. However, it has also been observed that cells carrying some tumor-promoting mutations are eliminated by wild-type tissue. It currently remains unclear what happens at the interface between normal and transformed cells. A complex interplay between oncogenes activation and environmental constraints regulates tissue cohesion during early tumorigenesis.
We aim to investigate the crosstalk of mechanical and genetics factors on the tissue cohesion during early tumorigenesis. Our approach consists in studying the dynamics at the interface between normal and precancerous cells in relation with its environment: mechanical state and oncogene activity. To assess different steps in tumor progression, we chose two oncogenes: RasV12A will promote cell proliferation while SrcY527F will promote metastasis dissemination.
First, we will create light-inducible oncogenes in order to control, in time and space, the level of oncogene activation. Combined with our expertise in nanofabrication, we will be able to finely position the transformable cells in a tissue of normal cells. Using tools from physics (laser ablation, microfluidics and nanofabrication), we will both characterize and disturb the mechanical environment of the transformed cells.
Altogether, we should be able to model and image the early stages of tumor development with an unparalleled degree of control.
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