Objective
Many signaling pathways in human cells involve lipid recognition events. The phosphorylation state of these lipids is under the control of both lipid kinases and lipid phosphatases. The phosphorylated second messenger lipids recruit lipid adaptor molecules, which regulate fundamental cellular processes including cell survival, proliferation, motility, differentiation and intracellular trafficking. Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate the 3’ hydroxyl group of inositol phosphate. The class IA PI3K family is associated with diseases including cancer, thrombosis, allergies and arthritis. Although it is clear that these PI3Ks are activated by Receptor Tyrosine Kinases (RTKs), PI3Kβ is the single member of the PI3Ks that is activated downstream of both RTKs and G-protein coupled receptors (GPCRs).
Using a combination of X-ray crystallography, in vitro activity assays and cellular experiments, I want to characterise the mechanisms specific to PI3Kß regulation. A first step will consist in the determination of PI3Kß structures in complex with G-protein ßγ heterodimers and with the small GTPase Rab5. That structural information will serve as an invaluable framework for further design of in vitro and cellular experiments to interrogate the exclusive mechanism of PI3Kβ regulation.
Because of the potential role of PI3Kβ in oncogenesis and thrombosis, I will also determine the structures of PI3Kß in complexes with a panel of PI3K isoform-specific inhibitors. These structures will provide the basis for the next generation of therapeutics.
This project will weave threads of structural, biophysical, biochemical and cell biology into a tapestry that depicts the roles of this unique enzyme that stands at the cross-road of RTK and GPCR signalling.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine rheumatology
- medical and health sciences clinical medicine angiology vascular diseases
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine allergology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-IEF
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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.
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.
Coordinator
W1B 1AL LONDON
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.