Přehled

Supervisor: Jozef Hritz, Ph.D.

Consultant: prof. Lukas Žídek, Ph.D.

Annotation:
The main neuropatological signs of Alzheimer disease are associated with the fibrillization of tau protein into neurofibrillar tangles. Studying of how different factors influence the formation of protein fibrils is the key for understanding these neurodegerative processes. The main aim of this PhD project will be characterization of conformational changes in the formation of tau fibrils due to their truncations, phosphorylation and the interaction with 14-3-3 proteins. Interdisciplinary approach combining biomolecular NMR, biophysical interaction techniques and computational methods will be applied. The described activities are part of international research projects allowing to spend the part of PhD study at the groups of our collaborators in Europe or North and South America and to learn specific research techniques, there.

Literature:

  1. Lippens, G., and Gigant, B. Elucidating Tau function and dysfunction in the era of cryo-EM. J. Biol. Chem. 2019, 294, 9316–9325.
  2. Přecechtělová, J.; Mládek, A.; Zapletal, V.; Hritz, J.: Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins, JCTC 2019, 15, 5642-5658.
  3. Melková, K.; Zapletal, V.; Jansen, S.; Nomilner, E.; Zachrdla, M.; Hritz, J.; Novácek, J.; Zweckstetter, M.; Ringkjøbing-Jensen, M.; Blackledge, M. and Žídek, L.: Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics.J. Biol. Chem. 2018, 293, 13297-13309.
  4. Nagy, G., Oostenbrink, C., and Hritz, J. Exploring the binding pathways of the 14-3-3ζ protein: Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints. PLoS One 2017, 12, 1–30.
  5. Motáčková, V., Nováček, J., Zawadzka-Kazimierczuk, A., Kazimierczuk, K., Žídek, L., Šanderová, H., Krásný, L., Koźmiński, W., and Sklenář, V. Strategy for complete NMR assignment of disordered proteins with highly repetitive sequences based on resolution-enhanced 5D experiments. J. Biomol. NMR 2010, 48, 169–177.

Keywords: Molecular Biophysics, tau protein, phosphorylation, 14-3-3 proteins, neurodegenerative diseases, NMR, computational simulations

General information about CEITEC PhD School – Life Sciences and Molecular Medicine: http://ls-phd.ceitec.cz/

Contact: phd@ceitec.muni.cz