Project: Modulation of protein-DNA and protein-protein interactions by small molecule compounds.
Research group: Biophysical Chemistry
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Deadline is closed
Modulation of protein-DNA and protein-protein interactions by small molecule compounds.
Contact person and project supervisor: prof. Tomas Obsil, obsil@natur.cuni.cz
WWW: http://web.natur.cuni.cz/~obsil
Research group: Biophysical Chemistry
Leader of the research group: Prof. RNDr. Tomáš Obšil, Ph.D.
Project summary:
The members of the Forkhead box (FOX) family of transcription factors share a conserved winged-helix DNA-binding domain (DBD) known as the Forkhead domain. The “O” subclass of FOX family consists of four proteins (FOXO1, FOXO3, FOXO4 and FOXO6), which regulate cellular homeostasis, longevity and response to stress. FOXO proteins were initially considered potent tumor suppressors; however, recent studies indicated that FOXO proteins can also promote tumor development and progression by maintaining cellular homeostasis and by inducing drug-resistance. Therefore FOXO proteins are considered potential drug targets for drug resistance prevention in cancer therapy. The team lead by prof. T. Obsil participates in an international collaboration aimed at development of small molecule compounds that would modulate FOXO transcriptional program by interfering with protein-DNA and protein-protein interactions of FOXO proteins [eLife 2019;8:e48876]. The goals of this PhD project are: (i) to study interactions between FOXO proteins and prepared compounds; and (ii) to characterize the ability of prepared compounds to inhibit protein-DNA and protein-protein interactions of FOXO proteins using various biophysical approaches. The results will provide a structural basis for modulating FOXO functions and help in further development of specific FOXO inhibitors.
Profile of an ideal candidate: MSc. or equivalent in Chemistry, Biochemistry or a related field (required), good knowledge of English. Experience with nuclear magnetic resonance (NMR) and recombinant protein production.
Solution structure of the free FOXO1 DNA binding domain (Psenakova et al. (2019) Cells 8(9), 966).
Deadline is closed