Understanding the interplay between hypoxia signalling and hepatitis B virus replication
James attained his undergraduate degree in Medical Science, at the University of Birmingham in 2017. During his time there, he completed a summer vacation studentship in the laboratory of Professor Jane McKeating, winning funding from the Lister Institute of Preventative Medicine. This project sought to understand the relationship between APOBEC mediated cytidine-deamination and Hepatitis C Virus sequence diversity and pathogenesis.
James returned to Professor McKeating's group at Oxford in October 2017 to begin his DPhil studies on a NDM Prize Studentship funded project. James' project is investigating how the cellular microenvironment can influence viral replication. The liver is the site of replication for hepatitis B virus (HBV), and presents a naturally low oxygen environment for the virus to manipulate and exploit. The cellular response to low oxygen is orchestrated predominantly by hypoxia inducible factors (HIFs), which are heterodimeric transcription factors that regulate gene expression by binding to a hypoxia response element in the promoter of genes. James is looking to understand the relationship between HIFs and HBV replication at physiological oxygen levels, to try to identify how viral gene expression is regulated.
As well as HIFs, there are many other factors which regulate the response to low oxygen, covering a range of roles in: gene expression, DNA methylation, protein function and epigenetic modifications. James is now beginning to explore the role of other dioxygenases, and how host factors could regulate the viral epigenome and, in turn, influence viral transcription and pathogenesis.
Circadian control of hepatitis B virus replication
Zhuang X. et al, (2021), Nature Communications, 12
The CCCTC-binding factor CTCF represses hepatitis B virus enhancer I and regulates viral transcription.
D'Arienzo V. et al, (2021), Cellular microbiology, 23
Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter
Wing PAC. et al, (2021), Journal of Hepatology
Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS
Liu Y. et al, (2020), Genome Biology, 21
Synchronised infection identifies early rate-limiting steps in the hepatitis B virus life cycle.
Chakraborty A. et al, (2020), Cellular microbiology, 22