Objective
Research objectives and content
Cancer is commonly linked to aberrant proliferation and a failure of the transformed cells to differentiate. Activated proto-oncogenes are thought to provide continuous proliferation signals that enhance the growth of transformed cells. Conversely, transformation can also be achieved by preventing transactivation of genes or gene network that regulate cell growth and/or differentiation. A prototypic example is the dominant negative oncogene, v-erbA, a mutated thyroid hormone receptor (T3R) variant encoded by the avian erythroblastosis virus (AEV). V-erbA is thought to antagonize T3R function through constitutive binding to T3-response elements and occlusion of the endogenous receptor and/or by actively repressing (silencing) transcription. Whether and how v-erbA represses natural genes within their chromosomal loci is largely obscure due to the lack of model systems. Recently, the Stunnenberg lab has been able to demonstrate that v-erbA silences expression of the chicken Carbonic Anhydrase II (CAII) gene through a novel v-erbA response element (VRE) located in an erythroid-specific enhancer. By using in vivo and in vitro approaches, I propose to use this model system to unravel the molecular mechanisms by which v-erbA and its cellular counterpart c-erbA/T3R silence transcription and to assess the role of putative co- repressor proteins in his process. This system affords a unique opportunity to investigate not only the molecular basis of erythroleukemia but also the regulation of the targeted gene by wild type and mutated nuclear receptors. Training content (objective, benefit and expected impact)
The Stunnenberg group is among the leading in the receptor field. This study will provide novel insight in how gene transcription is regulated by Class II nuclear receptors, and in particular the role of v-erbA and T3R in repression and chromatin opening. Moreover, this system provides the opportunity to unravel the molecular basis of the erythroleukemia.
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 biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- 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 (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
6525 ED Nijmegen
Netherlands
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