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Content archived on 2024-05-29

Keeping the spindle in shape: identification and characterization of new components involved for spindle formation

Objective

During each cell division a cell needs to distribute the genetic material equally to two daughter cells. To segregate chromosomes the cell uses a macromolecular machine: the bipolar spindle.

A bipolar spindle forms also in vitro, in Xenopus M-phase egg extract, a system of extreme value to analyse the function of individual spindle components in a simplified context.

Pioneered studies in egg extract led to the mechanistic insight of the role of the small GTPase Ran during mitosis. Ran-GTP was shown to regulate microtubule nucleation by releasing the inhibitory effect of import adaptors from factors like TPX2, in the proximity of the chromosomes.

We have used the Xenopus extracts to identify additional Ran effectors involved in spindle bi-orientation. Amongst the proteins found, we identified a new protein, which during the course of our studies was reported to be over-expressed in human hepatocellular carcinoma (therefore called HURP).

In this project we want to:
- Characterise and analyse the molecular function and interplay of the newly identified component of the spindle both in vivo and in vitro.
- Identify new proteins potentially involved in spindle assembly.
- Discover potential relationship between deregulation of these proteins with specific types of cancer.

For this purpose we will employ both the Xenopus egg system and mammalian cell lines, in order to combine the in vitro biochemical experiments with the temporal and spatial requirements observed in vivo. Moreover, analysis of biological samples from different types of cancer will indicate possible links of the proteins to oncogenesis.

Given that mitotic defects and aneuploidy is a crucial hallmark associated with high malignancy and poor prognosis of cancer, the outcome of the studies outlined in this proposal may acquire primary importance to our understanding of how mitotic errors can lead to cell transformation.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP6-2002-MOBILITY-11
See other projects for this call

Funding Scheme

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ERG - Marie Curie actions-European Re-integration Grants

Coordinator

DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, DEMOCRITUS UNIVERSITY OF THRACE, GREECE
EU contribution
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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