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The roles of 3-kinase isoforms in cell migration

Ziel

Phosphoinositide-3 kinases (PI3Ks) are a family of signal transducing enzymes that regulate a wide variety of cellular responses such as growth, proliferation, survival, cytoskeletal changes and cell migration. Deregulated PI3K signalling is implicated in cancer, inflammation and diabetes, and intervention with PI3K signalling is being pursued by the pharmaceutical industry. Mammals have 8 distinct PI3K isoforms, the individual roles of which are not well understood. Clinical intervention with PI3K signalling will almost certainly have to be targeted at individual isoforms, given the risk that global alteration of PI3K signalling will be deleterious to the organism. It is therefore critical to understand the roles of the PI3K isoforms at the cellular and organismal level.

This project aims to create and validate a leukocyte model system in which specific PI3K isoforms have been genetically inactivated and to delineate the functions of PI3K isoforms in vitro cell migration and signalling. More specifically, this project aims to derive primary and immortalised macrophages from gene-targeted mice in which PI3K isoforms have been inactivated in a constitutive or conditional manner, and to phenotypically characterise these cells, addressing the following important fundamental questions in cell biology and signalling:
1. which signalling programmes are controlled by individual PI3K isoforms?
2. which PI3K isoforms are critical for cell migration?
3. do specific PI3K isoforms control cell polarity?

This postdoctoral training period will allow me to train in important areas of cell biology and signal transduction, and allow to familiarize myself with advanced and unique approaches used by the Host Laboratory, including mouse gene knockouts and sophisticated cell biology and biochemistry. This postdoctoral period will also provide me the opportunity to build an international network of scientific contacts in academia and industry and to become an independent.

Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-5
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LUDWIG INSTITUTE FOR CANCER RESEARCH
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COURTAULD BUILDING, 91 RIDING HOUSE STREET
LONDON
Vereinigtes Königreich

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