Objectif "Phosphoinositide 3-kinases (PI3Ks) are a conserved family of lipid kinases that generate lipid second messengers inside cells. Mammals have 8 isoforms of PI3K, divided in three classes (I, II and III). The focus of research has thus far almost exclusively been on class I PI3Ks, which have been implicated in cancer, inflammation and diabetes and which are the target of ongoing drug development efforts in Pharma. Very little is known about the other PI3Ks, in particular the class II PI3Ks, which comprises the PI3K-C2alpha, PI3K-C2beta and PI3K-C2gamma isoforms. This research proposal aims to delineate the physiological roles of PI3K-C2alpha and PI3K-C2beta, their integration in signalling by tyrosine kinases and G protein-coupled receptors, the lipid products they produce in cells and their downstream intracellular signalling pathways. The focus of these studies will be on metabolic signalling and cancer. For this proposal, I have access to two new unpublished mouse lines with inactivating mutations in the PI3K-C2alpha and PI3K-C2beta genes, which will be subjected to whole-organism studies and phenotypic screening, in parallel to cell-based studies using various techniques, including new proteomic techniques which have been developed in the Host Laboratory. The Host Laboratory uses an innovative mouse gene targeting strategy whereby PI3K isoforms are inactivated in a ""drug-like"" fashion. This is achieved by the replacement of the wild-type gene by a germline knock-in allele that encodes a kinase-dead protein, mutated in the ATP-binding site. The proposed work is expected to uncover the biological roles of an evolutionary conserved signalling module. This work also has potential implications for the ongoing drug development in the PI3K area where inhibitors often also hit class II PI3Ks. It is critical for further drug development to be able to assess what the possible biological impact is of such drug target profile." Champ scientifique medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencescell biologycell signalingmedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicineoncology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Appel à propositions FP7-PEOPLE-2009-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur QUEEN MARY UNIVERSITY OF LONDON Contribution de l’UE € 171 740,80 Adresse 327 MILE END ROAD E1 4NS London Royaume-Uni Voir sur la carte Région London Inner London — East Tower Hamlets Type d’activité Higher or Secondary Education Establishments Contact administratif Lucy Connolly (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
