| Grant number: | 11/23659-2 |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| Start date: | March 01, 2012 |
| End date: | August 31, 2016 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Ana Carolina Migliorini Figueira |
| Grantee: | Jéssica Christina Lóis de Oliveira Campos |
| Host Institution: | Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil |
| Associated scholarship(s): | 14/22215-1 - NEW SIGNALLING PATHWAYS MODULATED BY THYROID HORMONE RECEPTOR (TR) IN BREAST CANCER, BE.EP.DD |
Abstract Nuclear Receptors (NRs) are proteins that in the presence of small and hidrophobic molecules, which previously penetrated the target cell and reached the nucleus, become activated to initiate the cellular response. These receptors are responsible for some pathology as heart diseases, diabetes, high levels of cholesterol and obesity which have been called metabolic syndromes. Today it is known that NRs act as direct regulators of gene transcription. This regulation comprises receptor bound to DNA sequences, recruitment of co-regulators, transcription machinery, and other mechanisms. However, in the past few years, crosstalk and transrepression had been focus of many studies inside nuclear receptors. A better understanding about transcriptional indirect regulation is the new challenge inside the attempt of identify different nuances, which could result in new targets for those pathologies. In this way, if one different protein complex was formed and identified, it is possible to predict its dissociation, in an effort to manipulate this complex. Therefore, we could avoid many of the undesirable defects of common regulation. This research intends the mapping of unusual interactions that occur between the NRs TR and PPAR, and any other proteins inside cell nucleus and cytoplasm, besides the transregulation mechanisms. This map should be done through superexpression of the receptors in specific human's cells, which will receive ligands treatments. New protein complexes with these receptors will be immunoprecipitated. After that, the different proteins inside the complex will be identified by mass spectrometry. Further, experiments of transactivation will be performed in mammal cells, to result in better understanding of physiological responses with these proteins complexed or separated. The most abundant complexes will be studied by biochemical and biophysical techniques like CD, fluorescence, native gel, etc. Finally, regulation models of receptors TR and PPAR will be made in several conditions. | |
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