Why is the flavivirus RdRp in the nucleus?

Research Opportunity
PhD, Masters by Research, Honours
Department
Microbiology and Immunology
Location
Doherty Institute
Primary Supervisor Email Number Webpage
Professor Jason Mackenzie jason.mackenzie@unimelb.edu.au (03) 9035 8376 Personal web page

Summary So what is this protein doing in the nucleus of a flavivirus? Is it affecting the innate immune response, cell transcription, metabolism or some other modification of host/viral RNA or proteins? During this project you will hopefully figure this out.

Project Details

Arguably all (+)RNA viruses replicate in the cytoplasm and the flaviviruses, such as dengue, West Nile and Zika viruses are no exception. Yet surprisingly the viral encoded RNA polymerase (i.e. RdRp) NS5 protein localises to the nucleus. Intriguingly NS5 does have a nuclear localisation signal and mutation of this motif significantly impairs virus replication. So what is this protein doing in the nucleus? Is it affecting the innate immune response, cell transcription, metabolism or some other modification of host/viral RNA or proteins? During this project you will hopefully figure this out. We have a range of wild-type and mutant NS5 proteins that will be utilised to explore and decipher why the nucleus is involved in flavivirus replication. You will utilise high-end imaging and visualisation approaches to assess nuclear trafficking and also state-of-the-art biochemical approaches to elucidate binding partners of NS5 in the nucleus. You will combine these studies with proteins suppression via RNAi or CRISPR and assess the impact of NS5 on many of the host cellular pathways. Of particular importance will be to assess the immune competency of cells that contain wild-type and mutated NS5. Ultimately the aim is to identify compounds that can impede the transport of NS5 into the nucleus or attenuate the activity of NS5 in the nucleus to prevent and treat flavivirus infections.



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity



Research Opportunities

PhD, Masters by Research, Honours
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Microbiology and Immunology

Research Group / Unit / Centre

Mackenzie laboratory: Intracellular virus replication and innate immunity

Research Node

Doherty Institute

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