Přehled

Doctoral study program: Life Sciences

Supervisor: doc. RNDr. Mgr. Jozef Hritz, Ph.D.

Topic title: Structural and Functional Characterization of Tau Fibrils and

Their Regulation by Interaction Partners

Annotation:

Tau is an intrinsically disordered microtubule-associated protein that maintains neuronal structure and stability. Under pathological conditions, Tau undergoes structural transitions leading to aggregation into amyloid-like fibrils, a hallmark of Alzheimer’s disease, and related tauopathies. This PhD project will focus on the structural and functional characterization of Alzheimer’s disease-relevant Tau fibrils and their inhibition by regulatory binding partners. The 14-3-3 protein family, known to interact with phosphorylated Tau, represents a promising modulator of Tau fibrillization dynamics. Using an integrative approach combining biochemistry, cryo-electron microscopy, spectroscopy, and kinetic assays, the project aims to uncover how 14-3-3 proteins influence Tau assembly pathways and characterize the structure of AD-relevant Tau fibrils. The expected outcomes will advance our understanding of Tau aggregation, provide molecular-level insights into 14-3-3 regulation, and identify strategies for modulating Tau pathology in neurodegenerative diseases.

Recommended literature:

1.      Hochmair, J.; van den Oetelaar, M. C. M.; Ravatt, L.; Diez, L.; Lemmens, L. J. M.; et al. (2025) Stoichiometric 14-3-3-zeta binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation.
Communications Biology  8(1), 1139

2.      Guo, T.; Noble, W.; Hanger, D. P. (2017) Roles of tau protein in health and disease. Acta Neuropathologica 2017, 133(5), 665–704.

3.      Kučinskas, G.; Kozeleková, A.; Kráľová, K.; Volko, V.; Šedo, O.; Hritz, J. (2025) 14-3-3-zeta protein prevents formation of GSK3β-phosphorylated Tau protein fibrils. International Journal of Biological Macromolecules 202, 148222.

4.      Fitzpatrick, A. W. P.; Falcon, B.; He, S.; Murzin, A. G.; Murshudov, G.; Garringer, H. J.; Crowther, R. A.; Ghetti, B.; Goedert, M.; Scheres, S. H. W. (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 2017, 547(7662), 185–190.

5.      Shi, Y.; Zhang, W.; Yang, Y.; Murzin, A. G.; Falcon, B.; Kotecha, A.; van Beers, M.; Tarutani, A.; Kametani, F.; Garringer, H. J.; Vidal, R.; Ghetti, B.; Hasegawa, M.; Scheres, S. H. W.; Goedert, M. (2021) Structure-based classification of tauopathies. Nature 2021, 598(7880), 359–363.

Research area: Structural biology, protein fibrilization, protein-protein interactions, brain disorders

Keywords: Tau protein, Intrinsically disordered proteins, Protein fibrilization, 14-3-3 proteins, Cryo-electron microscopy, Neurodegenerative diseases

Funding of the PhD candidate:

In the academic year 2026/27 the net income of the CEITEC PhD School student is expected to be at least CZK 29,400 (approx. EUR  1215)

 

03/2026 – 2029:          MŠMT INTER-EXCELLENCE II, INTER-ACTION – LUAUS26268: Fluorine NMR spectroscopy as an efficient tool for the interaction analysis of multivalent proteins

2023 – 2026:                Horizont Evropa: HORIZON-WIDERA-2022-ACCESS-04 (ID: 68358): Alzheimer’s Disease Diagnostics Innovation and Translation to Clinical Practice in Central Europe (ADDIT-CE)

2024-04/2027              MŠMT JPND (ID:9F24003): Spatiotemporal transcriptome and proteome analysis of Synuclein pathology in Parkinson’s disease: Identification of cell type-specific vulnerability and tolerance mechanisms (4DPD-Omics)

Requirements for candidate:

Experimental Molecular Biophysics and/or structural biology

Information about the supervisor:

5 successfully graduated PhD students; 50 publications; International and National research projects

https://www.ceitec.eu/jozef-hritz-ph-d/u26252?page=publication

Start date: September 2026

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