Finding a cure for chronic hepatitis B: the science behind the cure

Background: Chronic infection with the hepatitis B virus (HBV) affects 257 million people worldwide. Every year nearly 900,000 people die of its complications – liver cirrhosis and liver cancer. Although antiviral treatment is available, it does not cure the infection and HBV in most cases rebounds after treatment is discontinued. Experimental therapeutics are in early development that aim to cure the infection, typically by combining antivirals with immune-modulators. HBV is a complex virus that interacts in multiple ways with the host immune system. As a result, the infection can present with different phenotypes in different people. New scientific understanding about the interaction between the virus and the host is required to drive the development of an HBV cure.
Among the millions of people infected with the HIV virus, around 7% also have HBV. The interaction between HBV and HIV is poorly understood and therefore it is uncertain whether immune-modulators may offer a viable therapeutic option against HBV in this group.

Aim: This PhD studentship will characterise the immunological (e.g., PD-1/PD-L1 expression) and virological (e.g., HBV genotype, HBV RNA load) profiles of patients with chronic HBV infection at different stages of their disease and will investigate host genetic determinants that may impact on these parameters (e.g., PD-1/PD-L1 genetic polymorphisms). A specific aim will be to study the impact of HIV co-infection and its treatment on the HBV-related immunological and virological parameters to understand how HBV/HIV co-infected patients may respond to a future HBV cure.

Objectives:
1) To study the relationship between the HBV genome and virological and immunological parameters of HBV infection
2) To study the relationship between the host genome and virological and immunological parameters of HBV infection
3) To define how these parameters are modulated by HIV co-infection and HIV treatment
Note: The details of the study plan will be discussed with the candidate to personalise the areas of interest.

Samples: Human whole blood, serum, plasma, and peripheral blood mononuclear cells collected from patients with chronic HBV infection (including patients with HIV co-infection), and healthy volunteers.
Ethics: Ethics approval UoL001386.
Timescale:
Year 1: Assay development (HBV genome sequencing; host genome sequencing); sample collection; flow cytometry training
Year 2: Sample testing of virological and immunological parameters and genetic profiles
Year 3: Analysis and write up

Training Potential: There will be opportunities to learn about a new exciting area of research, to develop an integrated view of the interaction between host and virus, and acquire new scientific evidence to support the development of an HBV cure for people with and without HIV co-infection.
Techniques: Nucleic acid amplification and detection (e.g., real-time PCR); nucleic acid sequencing and sequence analysis (including phylogenetics); flow cytometry (immune-phenotyping); EIA
Research Methods: Laboratory techniques; ethics and governance of human research; database handling; phylogenetics; statistical methods
General: Verbal and written communication skills; team work; scientific liaisons

Please direct any enquires to:
Professor Anna Maria Geretti ([Email Address Removed])
Andrew McCallum ([Email Address Removed])
Harrison Austin ([Email Address Removed])

To apply, please send CVs, References, and Cover letters to [Email Address Removed]