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Combining protein engineering, biochemical and genetic approaches to dissect Par-1 function and regulation in vivo.

Ziel

The establishment and maintenance of cell polarity is a fundamental feature of most eukaryotic cells and is crucial for the generation of cell diversity through asymmetric cell divisions in development and for the proper execution of vectorial cellular fun ctions. Par-1 kinases play instrumental roles in cell polarization from yeast to humans. However, little is known about the molecular mechanisms by which they exert their effects. The Drosophila oocyte, which is ideally suited for genetic and biochemical m anipulation, will be used as a model system to identify and characterize Par-1 targets and regulators. Specifically, a proteomic-level screen will be applied to identify Par-1 targets. In parallel, candidate molecules likely to regulate or effect Par-1 fun ctions will be examined. Finally, new tools, including Par-1 activity sensors, will be developed to monitor Par-1 regulation in vivo. Given the molecular and functional conservation of Par-1 in eukaryotes, it is likely that interacting partners isolated in Drosophila will have similar functions in other organisms, providing insight into the molecular networks through which a fundamental process such as cell polarization is achieved. The host laboratory has extensive expertise both in doing state-of-the-art Drosophila genetics, as well as in developing and exploiting new approaches, demonstrated by multiple publications in top-tier journals. Furthermore, the interdisciplinary and highly interactive environment at EMBL, as well as its state-of the-art Core Fac ilities, provide a unique opportunity for receiving high-level training and doing cutting edge research in Molecular Biology. EMBL also offers great possibilities for collaborations and networking with scientists world-wide, contributing to the enhancement of European research. As my goal is to remain in Europe from now on, my transit through EMBL will be greatly beneficial for doing top-level science and starting an independent research career.

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FP6-2002-MOBILITY-5
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EUROPEAN MOLECULAR BIOLOGY LABORATORY
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