Overview

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

Supervisor: Gabriel Demo, PhD.

Annotation

Ribosome assembly is a complex, multi-stage process essential for cellular function. It involves the coordinated folding, modification, and binding of ribosomal RNAs (rRNAs) and proteins (r-proteins) with the assistance of various assembly factors. The absence or dysfunction of these factors often results in slow cell growth and improper ribosome assembly. Under such stress conditions, cells may employ stress-related factors to regulate ribosome assembly. However, the biological and structural connections between ribosome assembly and the stress response remain poorly understood compared to other aspects of ribosome function.

This thesis aims to unravel the intricate relationship between ribosome biogenesis and stress response mechanisms in bacteria and archaea. By analysing ribosomal fractions from bacterial strains lacking key maturation factors, we seek to identify novel ribosome-associated factors or repurposed translation factors involved in ribosome reassembly. Single-particle cryo-electron microscopy will provide structural insights into ribosome reassembly processes using ex vivo ribosomal complexes. Additionally, the investigation of the archaeal translation system, an understudied area, may reveal novel proteins linked to ribosome maturation. This research promises to uncover previously unknown mechanisms of ribosome reassembly in bacteria with defective ribosome maturation and identify novel factors influencing ribosome assembly in archaea.

Recommended literature

  • Klinge, S. and J. L. Woolford, Jr. (2019). Ribosome assembly coming into focus. Nat Rev Mol Cell Biol 20(2): 116-131.
  • Khusainov, I., et al. (2020). Mechanism of ribosome shutdown by RsfS in Staphylococcus aureus revealed by integrative structural biology approach. Nat Commun 11(1): 1656.
  • Sharma, I. M. and S. A. Woodson (2020). RbfA and IF3 couple ribosome biogenesis and translation initiation to increase stress tolerance. Nucleic Acids Res 48(1): 359-372.
  • Nikolay, R., et al. (2021). Snapshots of native pre-50S ribosomes reveal a biogenesis factor network and evolutionary specialization. Mol Cell 81(6): 1200-1215 e1209.
  • Yaeshima, C., et al. (2022). A novel ribosome-dimerization protein found in the hyperthermophilic archaeon Pyrococcus furiosus using ribosome-associated proteomics. Biochem Biophys Res Commun 593: 116-121.

Research area: RNA/nucleic acids research, translation regulation, ribosome reassembly, cryo-electron microscopy, structural biology

Keywords: RNA, translation, ribosome maturation, anti-association, cryo-electron microscopy, structural biology

Funding of the PhD candidate

The PhD student will receive support through active projects that are financially backed by grants focused on translation regulation mechanisms. These grants ensure full co-financial support for the PhD candidate’s salary.

Requirements for candidate

We are seeking a PhD. candidate who was trained in structural biology (mainly cryo-electron microscopy), worked in translation field or in general biochemistry and is a motivated person with collaborative mind set.

Information about the supervisor

Currently, Demo lab has several supervised students, including a third-year PhD student in Life Sciences, a Master’s student in Biomolecular Chemistry, and an undergraduate student in Biochemistry program. The lab is actively engaged in projects that focus on translation regulation, specifically investigating ribosome maturation and assembly mechanisms.

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

Application webpage: https://www.ceitec.eu/ribosome-assembly-mechanisms/t11435

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