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Mechanisms of Human Translation Control
Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)
Research area
Translation, Cryo-EM
Supervisor
Annotation
Co-translational quality control is triggered as a response to translational stalling events. Yet, different molecular mechanisms are employed for the recognition of these stalls and to trigger downstream rescue and quality control pathways. The use of collided ribosomes as a proxy for the recognition of translation problems in the cell is conserved from bacteria to humans. In eukaryotes, co-translational quality-control processes triggered by ribosome collisions accomplish several tasks and eventually trigger stress response signalling pathways. These tasks include the degradation of aberrant mRNAs, the degradation of potentially deleterious nascent peptides, the ribosomal subunit rescue and tRNA recycling. We mainly use structural analysis by cryo-EM to gain mechanistic understanding of these translational control events. To that end, we reconstitute macromolecular complexes involved in these processes in vitro or isolate them from cells.
The successful candidate will utilize a multidisciplinary approach to provide detailed mechanistic understanding of the critical human co-translational processes. 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.
Recommended literature
- Filbeck, S., et al., Ribosome-associated quality-control mechanisms from bacteria to humans. Mol Cell, 2022. 82(8): p. 1451-1466.
- Ikeuchi, K., et al., Collided ribosomes form a unique structural interface to induce Hel2-driven quality control pathways. EMBO J, 2019. 38(5).
- Saito, K., et al., Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria. Nature, 2022. 603(7901): p. 503-508.
- Narita, M., et al., A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation. Nat Commun, 2022. 13(1): p. 6411.
- Wu, C.C., et al., Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate. Cell, 2020. 182(2): p. 404-416 e14.
Funding
ERC StG / EMBO IG
Requirements on candidates
The ideal candidate should have background in either molecular biology, biochemistry or structural biology. Experience with human cell culture work, RNA biochemistry or protein expression and purification is a strong 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.