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.During my UK post-doctoral training funded by EIF, I have created and characterized new mouse models targeting one isoform of PI3K, p110beta, which physiological role was unknown. Isoform-specificity of p110beta in cell signalling, and in physiology, in particular in angiogenesis, was investigated using these gene-targeted mice. These results led to a revisited classification of PI3Ks.PI3K signalling is altered (constitutively active) and correlated with a poor pronostic in pancreatic adenocarcinoma. Pancreatic adenocarcinoma is one of the most lethal cancers and no chemotherapeutic treatment is currently available for this type of cancer. In this proposal, I will study the isoform-specific role of the signalling enzymes PI3Ks using new unique mouse models created and characterised during my post-doc in which each isoform of PI3K is genetically inactivated. While PI3K inhibitors are already tested in clinical trials for cancer applications, the implication of the different isoforms of PI3K in cancer is still unclear and intensely debated. This project targets to increase the understanding of the complex relationship within the different isoforms of PI3K in cancer cell signalling in vivo, in order to better target and prevent secondary effects in this clinical context.This re-integration period in Toulouse, France, will allow me to be familiarized with mouse pancreatic models used by the Host Group. Having secured a permanent position as a junior scientist in the Host team, I aim to integrate myself in this new cancer research environment and to develop my independence inside this group by implementing this project on a “hot” topic in cancer research.