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Role of Aurora A kinase in establishment and maintainance of spindle bipolarity during mitosis

Objectif

To be faithfully transmitted during cell division, chromosomes segregate on the mitotic spindle. The spindle assembles by the separation and migration of the two centrosomes nucleating microtubules either side of the condensed chromosomes. Aurora A kinase, whose gene is a human cancer susceptibility gene, appears necessary for correct spindle assembly. Nevertheless, how it orchestrates the process is not fully understood.

We propose to study roles of Aurora A in regulating spindle function through motor com plexes and microtubules associated proteins responsible for the migration of centrosomes. The aim of this project is first to analyse the defects in mitotic spindle formation in living drosophila embryo mutant for Aurora A or injected with Aurora A inhibitors (molecules tested as anti-cancer agents in pre-clinical studies at Cyclacel Ltd).

Secondly, I will study the role of Aurora A phosphorylation on potential substrates of the kinase associated with microtubules. I will use mass spectrometry to identify the phosphorylation sites. I will then mutate these sites and determine the effects upon assembly of the mitotic spindle. This project fits to a thematic priority of the FP6 program, namely to combat cancer.

The combined use of embryo imaging, Drosophila genetics and biochemistry will allow us to understand fundamentals of a biological process of therapeutic interest in cancer treatment. The main skills required for this project are totally new for me as my former experience was in the characterisation of the IGF-1 signal transduction pathway by means of biochemical and cellular biological approaches in Huntingtons disease.

Thus I am switching fields and joining a leading cell cycle group where I will become familiar with new methods and techniques. The opportunity to carry out my postdoctoral training at the University of Cambridge places me in a renowned and stimulating scientific environment that will be of great benefit to my growth as a scientist.

Champ scientifique (EuroSciVoc)

Mots‑clés

Thème(s)

Appel à propositions

FP6-2005-MOBILITY-5
Voir d’autres projets de cet appel

Régime de financement

EIF - Marie Curie actions-Intra-European Fellowships

Coordinateur

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Contribution de l’UE
Aucune donnée
Coût total
Aucune donnée