Share
Bunyavirus Replication-Transcription Complexes and Their Interplay with Host Translation Machinery
Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)
Supervisor
Annotation
Bunyaviruses are medically important negative-strand RNA viruses whose replication and transcription are mediated by the multifunctional RNA-dependent RNA polymerase (L protein) and viral nucleoproteins (NPs). Recent cryo-electron microscopy studies have revealed the molecular architecture and conformational dynamics of bunyaviral L proteins during RNA synthesis, yet the mechanisms coordinating viral transcription with host translation remain poorly understood. Emerging evidence suggests that viral replication-transcription complexes may localize in proximity to host ribosomes and translation factors, potentially facilitating efficient viral gene expression.
The primary aim of this project is to determine how bunyavirus L proteins, nucleoproteins, and ribonucleoprotein complexes interact with host translational machinery during infection. Initial studies will employ sucrose-gradient polysome profiling, immunoblotting, and mass spectrometry to identify associations between viral replication-transcription factors and host ribosomes or translation factors. Purified viral and host components will be used in biochemical binding assays to validate direct interactions and define minimal interaction networks.
To investigate these interactions under physiologically relevant conditions, a minimal bunyavirus replication-transcription system will be established in mammalian cell lines using viral minigenome approaches. Structural characterization of identified complexes will be pursued using single-particle cryo-electron microscopy and cryo-electron tomography, enabling visualization of viral ribonucleoproteins and associated host translation components. These studies will provide mechanistic insight into how bunyaviruses coordinate RNA synthesis and translation, potentially uncovering novel targets for antiviral intervention.
Recommended literature
- Wang X. et al. Structure of Rift Valley Fever Virus RNA-Dependent RNA Polymerase. Journal of Virology (2022).
- Arragain B. et al. Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes. Nature Communications (2020).
- Arragain B. et al. Structural snapshots of La Crosse virus polymerase reveal novel insights into replication and transcription mechanisms. Nature Communications (2022).
- Vogel D. et al. Structural and functional characterization of the Severe Fever with Thrombocytopenia Syndrome Virus L protein. Nucleic Acids Research (2020).
- Williams H.M. et al. Structural insights into viral genome replication by the Severe Fever with Thrombocytopenia Syndrome Virus polymerase. PLoS Pathogens (2023).
Research area
RNA/nucleic acids research in infectious diseases; structural virology; host-pathogen interactions; cryo-electron microscopy; translation regulation.
Keywords
Bunyaviruses; RNA-dependent RNA polymerase; L protein; nucleoprotein; ribosome; translation regulation; viral replication; cryo-EM; cryo-ET; host-pathogen interactions.
Funding of the PhD candidate
The PhD candidate will be financially supported through currently active research grants held by the supervisor, focused on structural studies of translation regulation and cryo-electron microscopy-based investigations of RNA-protein complexes. Funding covers the student's salary, consumables, access to state-of-the-art cryo-EM infrastructure, and international scientific collaborations.
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)
Requirements for candidate
We are seeking a highly motivated PhD candidate with an MSc degree in structural biology, biochemistry, virology, or a related field.
Preferred qualifications:
- Experience in molecular biology, biochemistry, or virology.
- Practical laboratory experience with protein purification, human cell cultures, or RNA biology.
- Basic knowledge of structural biology techniques, particularly cryo-electron microscopy.
- Interest in host-pathogen interactions and viral gene expression.
- Ability to work independently and collaboratively in an interdisciplinary environment.
- Good written and spoken English.
PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact Gabriel Demo (gabriel.demo@ceitec.muni.cz) for informal discussion.
Information about the supervisor
I (Gabriel Demo) am a structural biologist whose research focuses on translation regulation, ribosome biology and cryo-electron microscopy. The group has published multiple studies on translation regulation in bacteria and archaea, as well as structural work on the bunyaviral RNA-dependent RNA polymerase (L protein). Current projects investigate ribosome assembly regulation in bacteria, translation silencing in archaea, and the replication and transcription mechanisms of bunyaviruses. I have successfully supervised two BSc and two MSc students, currently supervising two PhD students, and one PhD student is expected to defend in Spring 2027, while an additional BSc student will join the laboratory in September 2026. The laboratory provides access to state-of-the-art cryo-EM infrastructure, interdisciplinary expertise, and a strong international research network in structural biology, translation, and virology.