4.1. 2018, Strukturní biologie signálních proteinů

PhD project: Molecular mechanisms of 14-3-3 proteins in signaling complexes     

14-3-3 proteins have the ability of binding the functionally different signal proteins, including kinases, phosphatases and transmembrane receptors by changing their function. Through the functional modulation of a wide range of binding partners, 14-3-3 proteins are involved in many important physiological and pathophysiological processes, including cell cycle regulation, metabolism control, apoptosis, and control of gene transcription.

The scope of this PhD project lies in the field of structural biology/biophysical chemistry. The main focus will be on elucidation of mechanisms by which the 14-3-3 proteins regulate their binding partners using a wide range of biophysical approaches. The work plan of the project contains preparation of recombinant proteins, biochemical and biophysical characterization of protein-protein interactions, and structural characterization of selected protein complexes, using protein crystallography, small angle x-ray scattering (SAXS) and fluorescence spectroscopy. Cooperation with the Faculty of Science, Charles University in Prague

Candidate´s profile (requirements): Successful candidate should enjoy working in the field of structural biology/biophysics/physical chemistry, be curious and has the courage to try out new things. Required is M.Sc. degree with the defense until June 2018 (fields: Chemistry, Biochemistry, Molecular Biology or similar). The knowledge of molecular biology, protein expression and purification is a strong advantage. Good knowledge of English is required.

We offer: friendly, motivating environment, part-time/full-time contract for 3 years with the possibility of renewal, 5 weeks of vacation, subsidized lunch.

Relevant publications:

• Alblova M, Smidova A, Docekal V, Vesely J, Herman P, Obsilova V, Obsil T. (2017) Molecular basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1. Proc Natl Acad Sci USA. doi: 10.1073/pnas.1714491114. PMID: 29087344.
• Kalabova D, Smidova A, Petrvalska O, Alblova M, Kosek D, Man P, Obsil T, Obsilova V. (2017) Human procaspase-2 phosphorylation at both S139 and S164 is required for 14-3-3 binding. Biochem Biophys Res Commun. 493:940-945.
• Kylarova S, Kosek D, Petrvalska O, Psenakova K, Man P, Vecer J, Herman P, Obsilova V, Obsil T. (2016) Cysteine residues mediate high-affinity binding of thioredoxin to ASK1. FEBS J. 283:3821-3838.  
• Kopecka M, Kosek D, Kukacka Z, Rezabkova L, Man P, Novak P, Obsil T, Obsilova V. (2014) Role of the EF-hand like motif in the 14-3-3 protein-mediated activation of yeast neutral trehalase Nth1. J Biol Chem. 289:13948-13961.

Supervisor:  RNDr. Veronika Obšilová, Ph.D.