Thesis topic proposal
György Vámosi
Interaction of nuclear receptors and their cofactors studied by modern fluorescence microscopy tools


Institute: University of Debrecen
theoretical medicine
Doctoral School of Molecular Medicine

Thesis supervisor: György Vámosi
Location of studies (in Hungarian): Department of Biophysics and Cell Biology, UD
Abbreviation of location of studies: DEBSI

Description of the research topic:

Retinoic acid receptor (RAR) and retinoid X receptor (RXR) are nuclear receptors activated by ligands of lipid nature, which regulate several physiological processes (lipid metabolism, proliferation etc.). According to the molecular switch model of nuclear receptor function, receptor dimers binding to the regulatory region of the target gene associate with corepressor in the absence of ligand and inhibit gene transcription, whereas in the presence of agonist they associate with a coactivator resulting in transcription. Data on receptor function are mainly derived from classic biochemical and molecular biological experiments on cell populations, and little is known about the dynamics and cell-to-cell variability of the processes. We aim to study receptor-receptor and receptor-cofactor interactions at the single cell level with single molecule sensitivity to be able to characterize the formation and kinetics of repression and activation complexes. We created receptors and cofactors tagged with fluorescent proteins (GFP, mCherry), and study their protein-protein and protein-DNA interactions by fluorescence microscopy techniques such as Förster resonance energy transfer (FRET) and fluorescence (cross)correlation spectroscopy. Genomic binding sites are mapped with ChIP-seq. Our work is done in collaboration with the Nuclear Receptor Research Group (László Nagy) at the Department of Biochemistry and Molecular Biology.

Required language skills: angol
Number of students who can be accepted: 1

Deadline for application: 2016-10-17

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