PhD Topics

1. Characterization of biomolecules in living cells using NMR spectroscopy

Supervisor: Lukáš Trantírek, Ph.D.

Annotation:
Advisably including methodical approaches and alternative directions in research.

“Most knowledge of protein structure and function is derived from experiments performed with purified protein resuspended in dilute, buffered solutions. However, proteins function in the crowded, complex cellular environment. The evidence demonstrates that protein behaviour in isolated solutions deviates from behaviour in the physiological environment.“

The candidate task will be to elucidate protein structure, dynamics, and interactions in the intracellular environment of living human cells using state-of-the-art in-cell NMR spectroscopy. The research focuses at quantitative assessment of the protein behaviour under various cellular states (e.g., in individual phases of the cell cycle, senescence, apoptosis, …). The project aims at development of general methodology allowing the early assessment of drug potency under physiologically relevant conditions.

Recommended literature:
Cohen R.D., Pielak G.J. A cell is more than the sum of its (dilute) parts: A brief history of quinary structure. Protein Sci. 2017 26(3):403-413.
Theillet, F.-X.; Binolfi, A.; Bekei, B.; Martorana, A.; Rose, H. M.; Stuiver, M.; Verzini, S.; Lorenz, D.; van Rossum, M.; Goldfarb, D.; Selenko, P. Structural Disorder of Monomeric α-Synuclein Persists in Mammalian Cells. Nature 2016, 530 (7588), 45–50.
Monteith WB, Cohen RD, Smith AE, Guzman-Cisneros E, Pielak GJ. Quinary structure modulates protein stability in cells. Proc Natl Acad Sci U S A. 2015, 112(6):1739-42.

Keywords: in-cell NMR spectroscopy; cell-cycle; drug screening; protein