POST-DOC POSITION to study the interplay between cell mechanics and epigenetics in CCM vascular malformations

A POST-DOC POSITION is available at the Institute for Advanced Biosciences (Grenoble, France) within the team” Physiology and Pathology of Invasions”, including 4 statutory researchers, 4 graduate students, 2 engineers CNRS and Master students. Our team coordinates a European ERA-NET consortium (France, Belgium, Germany, Italy, Slovakia). We tightly collaborate with clinical researchers, basic research teams, and with pharmaceutical/ biotechnology companies.

Research group: Mechanotransduction and Physiopathology of vascular malformations, Group leader: Eva Faurobert

When: Starting March 2025

Where: Institute of Advanced Biosciences (IAB) INSERM1209 CNRS5309 UGA

Website IAB: https://iab.univ-grenoble-alpes.fr

Duration: 18 months with possibilities of extension

Description :

Our lab focusses on the mechanical aspects of a cerebrovascular disease named Cerebral Cavernous Malformations (CCM) that is characterized by capillary-venous angiomas and recurrent bleedings. These vascular malformations form stacks of angiogenic and malformed capillaries composed of mosaics of mutant and wild-type endothelial cells (ECs). The goal of this proposal is to elucidate how cell mechanics and epigenetics interplay in controlling cell fate decisions in the CCM pathology. Our lab has shown that a loss of CCM proteins has a profound effect on EC mechanics and disrupts the mechanical homeostasis of the endothelium and the expression profile of numerous genes leading to a senescence associated with a secretory phenotype (SASP) (Vannier et al. Angiogenesis 2021). In a recent work, we showed that mechanically hyperactive senescent mutant ECs recruit wild-type ECs and reprogram them into proliferative cells (Shapeti et al. Nature Comm. 2024). How forces exerted by hyperactive mutant cells lead to reprogramming of neighboring cells remains unknown, a question also relevant in cancer and aging.

Job profile:

The goal of this post-doctoral work is to elucidate how cell mechanics and epigenetics interplay in controlling cell fate decisions in the CCM pathology and during aging. We will investigate how mechano-dependent epigenetic and transcription factors interplay in mutant and WT ECs and how mechanical inputs (ECM stiffness and fluid shear stress) regulate their dialog.

Level of study: PhD

Skills:

Theoretical training in cell biology, mechanotransduction, epigenetics, intracellular signaling.

Skills in cell culture techniques (transfection, lentiviral infection), molecular biology techniques (cloning, PCR, RT-PCR), cell imaging techniques (epifluorescence, confocal microscopy, live microscopy). Skills in microfluidic and/or micropatterning would also be highly appreciated.

We are seeking a highly motivated candidate for joining our dynamic and international team. Good communication in English and team playing skills are also required. Other skills include proficiency in data processing, good time organization.

How to apply: Applications, as a single PDF document containing a cover letter, a concise summary of

previous research, a Curriculum Vitae, a publication list and contact details for at least 2 references

should be sent to Eva Faurobert:

eva.faurobert@univ-grenoble-alpes.fr

The salary will be in accordance with the INSERM salary scale, depending on past experience. Social

security and health benefits will be included.