PhD topic / PhD position: The role of the intracellular environment in modulation of biomolecular...

Supervisor: Lukáš Trantírek

Annotation: The physical-chemical parameters of the intracellular space are actively contributing to regulation of biomolecular functions via influencing protein and nucleic acids structure and dynamics. While the coordinated and tightly controlled changes in the non-specific parameters of the intracellular space are permissive for broad range of fundamental physiological process including cellular division and differentiation, their deregulation leads to a number of human pathologies including cancer. The aim of this project is to explore a role of cellular environment in physiologically distinct cellular states on protein dynamics, structure and interactions with drug-like molecules.

The student will acquire advance knowledge and skills in human cell culture manipulations (cultivation, transfection, genome editing), DNA cloning, protein expression and purification, flow cytometry, confocal microscopy, and, in particular, with state-of-the-art in-cell NMR spectroscopy. The student will have the opportunity to present the results of his/her work at prestigious international conferences. Moreover, this project will involve collaboration with other leading researches in European institutes.

Prospective student should ideally have done masters in molecular/cellular biology, biochemistry, biomolecular chemistry, or biophysics. The experience with biomolecular NMR spectroscopy is advantage.  The most highly valued feature will however be excitement for science and strong drive in tackling important biochemical/biological, and biophysical questions.

Recommended literature:

• Broft P, Dzatko S, Krafcikova M, Wacker A, Hänsel-Hertsch R, Dötsch V, Trantirek L, Schwalbe H. In-Cell NMR Spectroscopy of Functional Riboswitch Aptamers in Eukaryotic Cells. Angew Chem Int Ed Engl. 2021;60(2):865-872.
• Krafcikova M, Dzatko S, Caron C, Granzhan A, Fiala R, Loja T, Teulade-Fichou MP, Fessl T, Hänsel-Hertsch R, Mergny JL, Foldynova-Trantirkova S, Trantirek L. Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy. J Am Chem Soc. 2019;141(34):13281-13285.
• Dzatko S, Krafcikova M, Hänsel-Hertsch R, Fessl T, Fiala R, Loja T, Krafcik D, Mergny JL, Foldynova-Trantirkova S, Trantirek L. Evaluation of the Stability of DNA i-Motifs in the Nuclei of Living Mammalian Cells. Angew Chem Int Ed Engl. 2018;57(8):2165-2169.
• Luchinat E, Barbieri L, Campbell TF, Banci L. Real-Time Quantitative In-Cell NMR: Ligand Binding and Protein Oxidation Monitored in Human Cells Using Multivariate Curve Resolution. Anal Chem. 2020 ;92(14):9997-10006.

More information on CEITEC PhD School website: https://ls-phd.ceitec.cz/ and Research Group website: https://www.ceitec.eu/non-coding-genome/rg109 . 

In case you are interested. ​Please, submit your CV and motivation letter via Registration Form .

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