Objective
The objective is to improve our understanding of (1) how errors in the segregation of chromosomes occur in mammalian cells, thus leading to aneuploidy, and (2) how segregational errors are caused by chemicals.
The chemicals of interest in this project include: chemotherapeutic agents, such as estramustine and dicarbazine; compounds of environmental relevance, such as vanadium salts and carbamate pesticides; alkylated biomolecules, whose study may shed some light on the mechanisms of action of the vast class of alkylating agents. The capacity of the chemicals to include aneuploidy is studied, when necessary, by in vitro tests, including conventional metaphase chromosome counting, fluorescence in situ hybridization (FISH) with centromeric DNA probes in interphase nuclei, and FISH or indirect immunofluorescence with antikinetochore antibodies in micronuclei. Various approaches are used to monitor the ability of chemicals to interfere with mitotic structures or to disturb specific pre-mitotic or mitotic events. High resolution video microscopy is used to monitor progression through mitosis of mammalian cell lines exposed to the chemicals of interest. This advanced technology allows detection of effects on early mitotic events, such as aster formation and migration and microtubule capturing by kinetochores, on chromosome movement both away from and toward the poles, and on late events, such as chromosome splitting at the onset of anaphase and spindle elongation. Confocal immunofluorescence and electron microscopy are used to clarify or confirm the effect of chemicals on specific steps of mitosis. An in vitro tubulin polymerization assay is used to study the effect of chemicals on the assembly/disassembly of microtubules. Progression through mitosis involves important changes in the state of phosphorylation of a number of cellular proteins. Interference of chemicals with protein phosphorylation is studied by assessing the phosphorylated state of indicator proteins (e.g. ribosomal protein S6) or of microtubule-associated proteins (e.g. MAP1A, associated to kinetochore).
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.
- natural sciences chemical sciences inorganic chemistry transition metals
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences earth and related environmental sciences environmental sciences pollution
- natural sciences biological sciences genetics chromosomes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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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
16132 Genova
Italy
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.