Overview

Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)

Research area
Translation

Supervisor
RNDr. Petr Tesina, Ph.D.

Annotation
Ribosome-associated quality control (RQC) is crucial for degrading truncated nascent proteins produced on aberrant mRNAs. Mutations in RQC components cause neurodegeneration both in animal models and human patients. Moreover, RQC insufficiency and subsequent protein aggregation critically contribute to proteostasis impairment and systemic decline during ageing.

The successful candidate will utilize a multidisciplinary approach to provide detailed mechanistic understanding of the critical human RQC system in combination with an in vivo study to reveal processes leading to RQC-driven pathological changes in neural tissue. He/she will utilize human cell cultures, protein expression and purification techniques and biochemistry methods to produce samples for cryogenic electron microscopy (cryo-EM). Comprehensive training in cryo-EM will be available to the successful candidate. The candidate will also have a unique opportunity to acquire expertise in the use of C. elegans as a model organism during a research stay at a collaborating laboratory in Bolzano (Italy).

Recommended literature
Tesina, P., et al., Molecular basis of eIF5A-dependent CAT tailing in eukaryotic ribosome-associated quality control. Mol Cell, 2023. 83(4): p. 607-621 e4.
Lu, B., Translational regulation by ribosome-associated quality control in neurodegenerative disease, cancer, and viral infection. Front Cell Dev Biol, 2022. 10: p. 970654.
Filbeck, S., et al., Ribosome-associated quality-control mechanisms from bacteria to humans. Mol Cell, 2022. 82(8): p. 1451-1466.
Udagawa, T., et al., Failure to Degrade CAT-Tailed Proteins Disrupts Neuronal Morphogenesis and Cell Survival. Cell Rep, 2021. 34(1): p. 108599.
Aviner, R., et al., Ribotoxic collisions on CAG expansions disrupt proteostasis and stress responses in Huntington’s Disease. bioRxiv, 2022: p. 2022.05.04.490528.
Funding
ERC StG / ERC CZ / Národní institut virologie a bakteriologie (LX22NPO5103) – Ministerstvo školství, mládeže a tělovýchovy ČR / Národní plán obnovy

Requirements on candidates
The ideal candidate should have background in either molecular biology, biochemistry or structural biology. Experience with human cell culture work or protein biochemistry is a plus.

Keywords
translation, cryo-EM, ribosome-associated quality control, co-translational control

Information on the supervisor
The supervisor has recently established the research group and is running the first round of hiring of PhD candidates.

Information about the application process
https://www.ceitec.eu/ls-mm-phd/

Application webpage
https://www.ceitec.eu/co-translational-quality-control-and-its-role-in-neural-tissue/t11439