PI 3-kinases (PI3Ks) are key signal transduction enzymes which are generally considered to be excellent new targets for therapeutic interference. Mammals have multiple PI3K isoforms. Here, I seek to investigate the role of the p110beta PI3K isoform in endothelial cells and angiogenesis, the growth of new blood vessels.
The functions and activities of endothelial cells depend on input from growth factors, chemokines and adhesion molecules. All of these agents are known to signal through PI3K. Indeed, there i s evidence for a role for PI3K activity in angiogenesis, but the roles of the distinct PI3K isoforms in this phenomenon are unknown.
Thus, I propose to investigate the role of the p110beta PI3K isoform in angiogenesis. I will use new PI3K mutant mice with a constitutively or conditionally inactive p110beta, which the Host Group has created (unpublished), and derived endothelial cells. At present, the physiological role of p110beta is completely unknown, and this PI3K isoform is one of the most enigmatic to d ate.
The Host Group has found that p110beta expression is highly enriched in endothelial cells, providing a strong indication of its role in this cell type. Other than work in vivo, the proposed work will also cover detailed mechanistic investigations at t he cellular level in isolated endothelial cells, complemented by the use of isoform-selective PI3K inhibitors developed with Host Group collaborations.
This post-doctoral period will allow me to be familiarized with advanced and unique approaches used by t he Host Group, including gene-targeted mice and sophisticated cell biology.
Other than widening my scientific horizon and allowing me to establish international contacts, this project will also widen my expertise in basic research to the field of angiogenesis in which I have developed a great interest.
It is my ultimate aim to continue my career the findings obtained from the proposed project by securing a future independent research position in France.
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