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PI3KC2

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Characterization of signalling and physiologic roles of the class II PI 3 kinase...

Characterization of signalling and physiologic roles of the class II PI 3 kinases "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 t... ver más

31/07/2012

QMUL

172K€

Presupuesto del proyecto: 172K€

Líder del proyecto

QUEEN MARY UNIVERSITY OF LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2012-07-31 No tenemos la información de la convocatoria

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1 Participantes

QMUL

0.00€ | Lider

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Líder del proyecto

QUEEN MARY UNIVERSITY OF LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 172K€

Fecha límite de participación Sin fecha límite de participación.

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 For this proposal, I have access to two new unpublished mouse lines with inactivating mutations in the PI3K-C2alpha and PI3K-C2beta genes, which will be subjected to whole-organism studies and phenotypic screening,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

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