Objective Correct chromosome segregation is an essential process in the mitotic cell division. This still poorly understood process occurs during mitosis and has recently been associated with cancer. The mitotic spindle is a complex structure regulated at multiple levels including the control of its formation by phosphorylation. Among the mitotic kinases, the Aurora family of proteins have specific roles in this process. Aurora A is a mitotic kinase commonly deregulated in human cancer and whose over-expression has been shown to induce mitotic defects, aneuploidy, and oncogenic transformation in vitro. However, the exact function of this protein is not well understood and we still do not know many of its substrates.In this project, we will develop a mouse model of Aurora-A inactivation by generating a conditional knock out for the Aurora-A (Stk6) gene. In addition, to investigate its role on tumour development and progression, we well generate a knock in mouse that will express a non-degradable form of this protein, and therefore resistant to its proteolytic degradation in mitosis. Both mouse models, for loss-of-function and gain-of-function, of Aurora-A will provide essential reagents to understand not only the biology of mammalian Aurora-A in vivo, but also for a better knowledge of the role in cancer of this protein, one of the few mitotic regulators that have been associated with tumour progression. Finally, this mouse model with altered mitotic regulation will be a valuable tool to improve current therapeutic strategies in cancer, mostly directed against mitotic progression. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticschromosomes Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Call for proposal FP6-2002-MOBILITY-12 See other projects for this call Funding Scheme IRG - Marie Curie actions-International re-integration grants Coordinator FUNDACIÓN CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS CARLOS III EU contribution No data Address Sinesio Delgado, 6 MADRID Spain See on map Links Website Opens in new window Total cost No data
