Research Projects
Molecular Basis of Hepatitis B Virus cccDNA Transcription and Maintenance

Objective and Significance:

Infection with hepatitis B virus (HBV) poses a major threat to public health in Hong Kong, China and other endemic areas, where more than 8% of all adults are chronically infected, resulting in an elevated risk of hepatocellular carcinoma (HCC). HBV has a small and partially double-stranded DNA genome of 3.2 kb, which forms a minichromosome in infected hepatocytes. The minichromosome contains covalently closed circular DNA (cccDNA), from which all viral RNAs are transcribed. cccDNA transcription controls the rate of HBV replication. Despite the availability and effectiveness of vaccines and anti-HBV drugs, cure of HBV infection is still not possible because cccDNA serves as the reservoir of viral DNA refractory to antivirals and accounts for viral relapse after cessation of antiviral treatment. To solve this problem it is necessary to understand how cccDNA is formed and maintained as well as how cccDNA transcription is regulated. Defining the molecular basis of cccDNA transcription and maintenance is fundamentally important in HBV research. In this project we will identify and characterize novel cellular proteins that are recruited to cccDNA to regulate its assembly and function. The molecular mechanism by which these proteins interact with long non-coding RNAs to switch on and off cccDNA transcription will be delineated. We will also shed light on the interplay between cellular regulator and viral transcription factor HBx. Finally, we will explore whether smallmolecule inhibitors of the cellular proteins might be developed as cccDNA-targeting agents to combat HBV infection. Our project will not only derive new knowledge in cccDNA biology, but will also reveal new strategies and compounds for prevention and therapeutic intervention of HBV-associated liver diseases.

Research Plan and Methodology:

Methods to study HBV transcription have been detailed in our recent paper listed below. Studies will be conducted in HBV-infected cells and cells transfected with a molecular clone of HBV genome. Standard procedures for molecular cloning as well as protein and RNA analysis will be used. The methods include dual luciferase assays; qPCR and RTqPCR; Southern, Northern and Western blotting; ELISA; co-immunoprecipitation; chromatin immunoprecipitation; confocal microscopy and biochemical fractionation.

Professor DY Jin, School of Biomedical Sciences

Biography
dyjin@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.