Objective
The mitotic checkpoint acts to inhibit entry into anaphase until all chromosomes havesuccessfully attached to spindle microtubules. Unattached kinetochores are believed to release inactivated form of proteins such as BubR1 and Mad2 that inhibits APC/C-dependent ubiquitinylation and subsequent proteolysis of components needed for anaphase onset.
Previous work by Dr. Abrieu(the host laboratory) has shown that the kinase Mps1 is required to recruit some checkpoint components onto the kinetochore, including CENP-E, a kinesin-like protein acting as a sensor of kinetochore to microtubules attachment. My work in this lab will consist on further dissecting the regulation of CENP-E by Mps1 in this context, using biochemical, chimiogenetic and microspectroscopic approaches. This will involve developing a new method to identify Mps1substrates; a multidisciplinary approach (chimiogenetic) in tight collaboration with the organic chemistry laboratory of Prof. Perigaud. I am also proposing to identify the minimal kinetochore binding domain of CENP-E. This will allow me to follow its activation, and regulation of the downstream kinaseBubR1 at the kinetochore by FRET (Fluorescence Resonance Energy Transfer). Finally, I will try to uncover new kinetochore proteins by fishing for binding partners of two outermost kinetochore components (CENP-E and Mps1) and the innermost centromeric protein (CENP-A). Altogether, this proposal should provide a better understanding of the checkpoint regulation at the kinetochore, a process whose deregulation is leading to aneuploidy, a hallmark of cancer.
Hopefully, these studies could lead to new therapeutic development specifically targeting cancer cells by directly activating checkpoint regulators, thus preventing side effects onto normal cells.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- agricultural sciences agriculture, forestry, and fisheries fisheries
- natural sciences chemical sciences organic chemistry
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
PARIS
France
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.