Chronic Hepatitis B: from virological concepts to cure

Summary

We are seeking passionate Ph.D. and Masters candidates to conduct a research project on understanding how hepatitis B virus persists in the liver to ultimately design a cure for chronic infections. 

We particularly encourage those from underrepresented groups (including women, First Nations People, people from a non-English speaking background, and people with disabilities) to apply.

Supervisor(s)

Dr Thomas Tu, Associate Professor Mark W Douglas

Research Location

Westmead - Westmead Institute for Medical Research

Program Type

Masters/PHD

Synopsis

Chronic infection with the Hepatitis B virus is the single greatest cause of liver disease worldwide (responsible for 300 million current infections and 833 000 annual deaths through liver cancer or cirrhosis). Patients typically are infected for life and the infection is currently incurable. The virus persists in the liver in a therapy-resistant form (closed circular DNA, cccDNA). 
To cure infection, cccDNA must be cleared. We have developed novel assays and have discovered new viral mechanisms that maintain cccDNA. The goal of this project is to disrupt these pathways, thereby curing the infection. 
Our project brings together broad expertise and collaborates with world-leaders in virus infection models, proteomics, virology, cell biology, gene therapy, and clinical practice. Our approaches are centred in basic science that underpins the development of new treatments.
We will use the following independent, but complementary approaches:
1. High-throughput screening of in vitro infection systems to find novel genes (and eventually drug candidates) that affect cccDNA.
2. Analysis of human patient samples to find novel biomarkers for cccDNA monitoring.
3. Deep characterisation (e.g. proteomics, RNAseq) of cells that maintain or degrade cccDNA to understand pathways to target for HBV cure.

Additional Information

Students working on this project can expect to learn the following techniques: CRISPR-Cas9-mediated gene editing, single-cell PCR, state-of-the-art microscopy, mathematical modelling, bioinformatics analysis, cell culture, virus production, animal handling, flow cytometry, and/or high-throughput screening assays.
About the Storr Liver Centre
The Westmead Clinical School's Storr Liver Centre focuses on the diverse range causes of liver diseases, including drugs and toxins, metabolic factors, and viruses. Internationally-acclaimed, the Centre has made outstanding contributions in defining the host responses to liver injury, understanding the underlying mechanisms of liver disease, and subsequent development of clinically-relevant bio-markers.
The Centre is well funded and employs cutting-edge techniques to bring each project to fruition. There will also be opportunities to collaborate with renowned researchers located both internationally and locally within the Westmead Institute for Medical Research. As part of the community of >400 researchers based on the Westmead hub, we are well equipped with state-of-the-art molecular, translational and cell biology facilities.

Want to find out more?

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Keywords

hepatitis B, Liver, Cancer, screening, infection, genomics, cure, therapeutics, Drug development

Opportunity ID

The opportunity ID for this research opportunity is: 2841

Other opportunities with Dr Thomas Tu

Other opportunities with Associate Professor Mark W Douglas