About the Project
Viral infections are ubiquitous in nature and are a major driver of host evolution. The outcome of infection is shaped by interactions between host and viral genomes, yet the mechanisms by which genetic variation in both species influences immune responses remain poorly understood. Recent advances in genomics and single-cell technologies provide an unprecedented opportunity to investigate these host–virus genetic interactions at cellular resolution.
For this DPhil you will work with Prof Katrina Lythgoe based in the Department of Biology, University of Oxford, and Dr Azim Ansari in the Department of Experimental Medicine, University of Oxford. During your DPhil, you will analyse data from a uniquely powerful cohort comprising over 200 individuals infected with Hepatitis C virus (HCV), for whom host genotype, viral whole-genome sequence, and newly generated single-cell transcriptomic and T-cell receptor (TCR) repertoire data are available. Previous analyses of this cohort have revealed strong genotype-by-genotype interactions between host innate immune genes and viral evolution. Viral sequencing has identified extensive within-host genetic diversity, including resistance-associated variants and highly structured viral populations, while host bulk RNA sequencing has identified marked differences in immune responses, including pronounced sex-specific transcriptional signatures. However, the cellular basis of these observations remains unresolved because bulk transcriptomic profiling cannot distinguish the contributions of individual immune cell populations or activation states.
Aims
You will use single-cell RNA sequencing and paired TCR repertoire profiling of peripheral blood mononuclear cells (PBMCs) to determine how host and viral genetic variation shapes gene expression and immune cell states across distinct cell populations. By integrating host genomics, viral genomics and single-cell immune profiling, the project will investigate how host–virus genetic interactions influence cellular phenotypes and adaptive immune responses. Depending on progress, additional aims could include determining whether specific antiviral or exhausted T-cell states are clonally expanded, investigating how host genetic variation influences T-cell repertoire diversity, and identifying associations between viral genetic variation and adaptive immune cell states.
Methods
The project will involve the development of new computational methods for integrating host and viral genomics with single-cell transcriptomic and immune repertoire data, and appropriate training will be provided. Together, this work will provide new insights into the fundamental genetic principles governing host–virus interactions and immune cell diversity, with broad relevance to understanding host–pathogen evolution.
Project code
KL02
Funding
This project is part of the DPhil in Biology programme, and is not a funded course at the University of Oxford; as such, students are expected to explore options for funding. However, we anticipate being able to offer around 6 full graduate scholarships to incoming DPhil students in 2027/28.
You will be automatically considered for several Oxford scholarships, which cover fees and stipend, if you fulfil the eligibility criteria and submit your graduate application by 6 January 2026. Scholarships are awarded based on academic achievement and potential to excel as a DPhil student.
For further details about searching for funding as a graduate student visit the graduate study information on our website.
Eligibility
For full entry requirements and eligibility information, please see the main admissions page.
How to apply
The deadline for applications for 2027/28 entry is 6 January 2027. We will continue to accept applications submitted after this date, but these late applications will not be considered for scholarship funding.
You can find the admissions portal and further information about eligibility and the DPhil in Biology Programme at the University's graduate admissions page. Please quote the Project Reference Code alongside the title in the 'Proposed field and title of research project, if applicable' field in the application form.
Institution website: https://www.biology.ox.ac.uk/dphil
References
Ansari et al (2017) Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus. Nature Genetics 49(5):666-673
Zhao et al (2025) Genetically Distinct within-host subpopulations of hepatitis C virus persist after Direct-Acting Antiviral treatment failure. PLoS Pathogens 21(4) e1012959