Objective
Research objectives and content
Met is a receptor tyrosine kinase that elicits multiple biological responses including cell growth, scattering and tubulogenesis The autophosphorylation of two neighbouring tyrosine residues Y1234 and Y1235 in the kinase domain upregulates catalytic' activity and results in the phosphorylation of two tyrosines located in the cytoplasmic C-terminal tail Y1349 and Y1356 the mediates high affinity interactions with the SH2 domains of a number of signal transducers. Met is overexpressed in; significant number of carcinomas and is amplified in metastases. A direct genetic connection between Met activation an/ human cancer was demonstrated recently by the identification of causal mutations in the Met kinase domain for hereditary and sporadic papillary renal carcinomas (PRC). Some of these mutations have been shown to constitutively activate the receptor and when expressed in fibroblasts, form foci of transformation. Furthermore, all of the Met papillary renal carcinoma mutation are tumourigenic in nude mice. Therefore, single mutations have been identified in MET that convert the proto-oncogene to an oncogenic counterpart. The aims of the proposed study are: (1) to analyse the signalling pathways used by the Met receptor harbouring PRC mutations; (2) to define the structural basis for the oncogenic activation of the Met kinase by the resolution ofthe crystal structures of the wild-type and mutated Met tyrosine kinase domains.
Training content (objective, benefit and expected impact)
The objective of the candidate is to gain experience in the research of receptor tyrosine kineses and intracellular signalling pathways and their relation to human neoplastic disease. Dr. Tracy Williams will benefit from working in a research laboratory with a distinguished history in this area of research in which all necessary expertise is available to provide a thorough training in this field. Dr. Williams will be integrated into the the Cancer Research Institute (I.RC.C.) in Turin, Italy, under the direction of Professor Paolo Comoglio and will be supervised by Dr. Alberto Bardelli. The data accummulated from the research proposal is expected to be published in high impact international journals. Links with industry / industrial relevance (22)
We have an established collaboration with Pharmacia which aims to block Met activation and signalling, the research proposal of the candidate is directly relevant to this collaboration.
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.
- engineering and technology materials engineering crystals
- natural sciences biological sciences cell biology cell signaling
- humanities history and archaeology history
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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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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
10060 CANDIOLO
Italy
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