Employer: Institut Curie
Location: Paris, France
A post-doc position for 3 years is now open in the Institut Curie, Paris France, in the Mechanics and Genetics of Embryonic and Tumoral Development biology/physics interdisciplinary team, aiming at studying the underlying mechanism of colonic tumorigenesis mechanical induction in vivo. The studies are based on the observation that on Drosophila embryos and mice colon tissues, developmental master genes [1, 2, 3] (embryos) and tumoral progression master genes  (colon cancer) expression is activated in response to mechanical strains.
Most recently, we have developed a unique method allowing to magnetize the mesenchemial conjunctive tissue of mice colon with ultramagnetic liposomes (UML), and to apply a magnetic pressure mimicking tumour pressure to the colon during weeks to months in vivo . Our results demonstrate the activation of the b-cat pathway and of downstream oncogenic processes from c-Myc, axin-2 and zeb-1 overexpression to ACF formation in healthy tissues. We have also found Ret kinase as mechanically activated upstream of b-cat, a mechano-sensor initiating b-cat activation for potential drug targeting.
The objective of the post-doc is to exploit our mechanical induction magnetic technology in vivo, to find the crypt cells involved in the mechanotransductive process and its associated underlying molecular mechanism. The project will be realized in the Institut Curie, and will combine the interdisciplinary and inter-institution expertise of 4 teams: Christine Ménager’s team (Paris6-ESPCI, UML production), Mickael Tanter’s team (Inserm-ESPCI, acoustic imaging), Didier Meseure (Pathologist, Institut Curie Hospital) and Emmanuel Farge’s team (Inserm-Institut Curie, mechanotranduction in vivo).
Contact: Emmanuel Farge:
- Scott, I.C., and Stainier, D.Y. (2003). Developmental biology: twisting the body into shape. Developmental biology: twisting the body into shape 425, 461-463.
- Desprat, N., Supatto, W., Pouille, P.A., Beaurepaire, E., and Farge, E. (2008). Forces Driven by Morphogenesis Modulate Twist Expression to Determine Anterior-Midgut Differentiation in Drosophila Embryos. Dev Cell 15, 470-477.
- Purnell, B. (2008). Editor’s Choice: Development: Giving a Twist to Twist. Science 322
- Whitehead, J., Vignjevic, D., Fütterer, C., Robine , S., and Farge, E. (2008). Mechanical factors activate β-catenin-dependent oncogene expression in APC1638N/+ mouse colon. HFSPJ 2, 286-294.
- Fernandez-Sanchez ME, Barbier S, Whitehead J, Béalle G, Michel A, Latorre-Ossa H, Rey C, Fouassier L, Claperon A, Brullé L, Girard E, Servant N, Rio-Frio T, Marie H, Lesieur S, Housset C, Gennisson JL, Tanter M, Ménager C, Fre S, Robine S, and Farge E. (2015) Mechanical induction of the tumourogenic beta-catenin pathway by tumour growth pressure. Nature, 523(7558):92-5. doi: 10.1038/nature14329. Epub 2015 May 11.