Objective
Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that generate intracellular second messengers in signal transduction and membrane trafficking pathways and are important drug targets. This proposal seeks to delineate the roles and mechanism of action of a group of PI3Ks which have remained enigmatic ever since their discovery over a decade ago.
The PI3K family comprises eight members in three subclasses. Class I PI3Ks signal downstream of growth factor and G protein-coupled receptors, are amongst the most commonly mutated genes in cancer and are being exploited as drug targets. The class II and III PI3Ks have in part emerged as regulators of membrane trafficking pathways but their physiological roles remain poorly understood.
We aim to identify the physiological roles of the class II PI3K-C2α and β and to characterize the impact of their kinase activity on signalling pathways. To analyse the roles of class II PI3K activity in vivo, the Host Laboratory has created constitutive global and conditional knock-in kinase-inactive mice (unpublished). In contrast to PI3K gene knockout models, these mouse lines allow us to specifically address kinase-dependent functions and hence are an ideal model to evaluate the potential of class II PI3Ks as drug targets.
The class II PI3K-C2α (C2α) is involved in endo- and exocytosis as well as endocytic recycling, whereas PI3K-C2β (C2β) has been implicated in cell migration. However, their influence on cellular signalling is unknown. As an initial approach, the Host Laboratory performed a screen for proteins interacting with C2α or C2β (unpublished). We will explore hits from this screen using the kinase-inactive knock-in mice and cells derived thereof as discovery tools.
The combination of my expertise in membrane traffic and phosphoinositide regulation with the mouse and signalling studies of the Host Laboratory form an excellent and timely basis to uncover the roles of the class II PI3Ks in mammalian biology.
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.
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 medical biotechnology genetic engineering
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine allergology
- medical and health sciences basic medicine physiology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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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.
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MSCA-IF-EF-ST - Standard EF
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2014
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WC1E 6BT LONDON
United Kingdom
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