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Molecular analysis of drosophila cell division

Molecular analysis of drosophila cell division

Objective

Mitotic errors and genome instability are major contributing factors to malignant transformation. Loss or gain of entire chromosomes, or stable chromosome fragments generated by all sorts of rearrangements, play an essential role in the unbalance of gene products that contributes to malignancy. The importance of aneuploidy in the progression of a cell to the cancerous state is well established. Aneuploidy can be generated by defects in either the kinetochore, the mitotic apparatus or the spindle checkpoint. Another mitotic structure that has been implicated in cancer etiology is the centrosome. Centrosome abnormalities have now been reported in many tumors and many oncogenes and tumor suppressor genes have been found to be associated with the centrosome at different stages of the cell cycle. Finally , it has been proposed that multinucleated cells produced by failure of cytokinesis would give rise to aneuploid mitotic products that would promote carcinogenesis The research to be undertaken is aimed at a further understanding of the molecular mechanisms that underlie genomic stability in higher eukaryotes.
The aim of this proposal is the study of the above topics using Drosophila melanogaster as a model organism. Using a variety of integrated genetic and biochemical approaches we plan to analyze
(1) the spindle checkpoint machinery,
(2) the regulation of centrosome activity,
(3) the centrosome and its interacting proteins and
(4) the mechanisms of cytokinesis. Given the high degree of evolutionary conservation of genes involved in cell division, our findings should provide the basis for identifying genes that govern the mitotic process in human cells. The discovery of such genes should extend our knowledge of cancer etiology and provide a potential basis for therapeutic intervention.

Coordinator

UNIVERSITY OF ROME "LA SAPIENZA"

Address

Piazzale Aldo Moro 5
00185 Roma

Italy

Administrative Contact

Pimpinelli PROF. SERGIO

Participants (5)

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ASSOCIACAO DO INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR

Portugal

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

CENTRO NACIONAL DE INVESTIGATIONES ONCOLOGICAS

Spain

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

Spain

University of Cambridge

United Kingdom

Project information

Grant agreement ID: HPRN-CT-2002-00260

  • Start date

    1 January 2003

  • End date

    30 April 2007

Funded under:

FP5-HUMAN POTENTIAL

  • Overall budget:

    € 1 196 309

  • EU contribution

    € 1 196 309

Coordinated by:

UNIVERSITY OF ROME "LA SAPIENZA"

Italy