Characterization of signalling and physiologic roles of the class II PI 3-kinases

Objective

"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 For this proposal, I have access to two new unpublished mouse lines with inactivating mutations in the PI3K-C2alpha and PI3K-C2beta genes, which will be subjected to whole-organism studies and phenotypic screening,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."

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• medical and health sciences basic medicine pharmacology and pharmacy drug discovery
• natural sciences biological sciences cell biology cell signaling
• medical and health sciences clinical medicine endocrinology diabetes
• natural sciences biological sciences biochemistry biomolecules lipids
• medical and health sciences clinical medicine oncology

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2009-IEF
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator