The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

EDUCATION

Research Projects

Project: Why is the flavivirus RdRp in the nucleus?

Mackenzie Group

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.

Contact project supervisor for further
information and application enquiries

Project Supervisor

Professor Jason Mackenzie

Project availability
PhD/MPhil
Master of Biomedical Science
Honours

Mackenzie Group

jason.mackenzie@unimelb.edu.au

1 vacancies

Themes
Host Pathogens Interactions
Immunology
Viral Infectious Diseases
Cross Cutting Disciplines
Discovery Research

The Mackenzie group investigates how viruses interact with the cells they infect. In particular the molecular and cellular processes that are manipulated by flaviviruses (dengue, Zika and West Nile viruses) and noroviruses for their own gain. We aim to understand how the intracellular events of virus replication result in innate immune evasion and ultimately how the consequences of infection result in a diseased state. Answering these questions will guide and inform us of areas for antiviral therapeutic development.


Mackenzie Group Current Projects