Biomarkers and Immunogenicity of the HIV reservoir in primary HIV infection

Project Overview

Background

The HIV reservoir is the primary barrier to a cure for HIV infection and is thought to be located predominantly within resting memory CD4 T lymphocytes. It is unclear whether these latently infected HIV+ cells express certain biomarkers (eg CD2, CD32, PD-1) or other key characteristics (eg antigen specificity) that may facilitate their investigation and targeting. Additionally, whether these latently infected cells can be targeted or suppressed by T or B cell-mediated, innate or innate-like immunity is unclear, as is whether effector cells can contain and control rebound viraemia.

 

Aims and Objectives

This project will explore ex vivo the characteristics of those cells which may contribute to persistent HIV infection. Undertaken in state-of-the-art facilities at the Peter Medawar Building in the University of Oxford, the project will combine flow cytometry, cell sorting and gene expression approaches (including RNAseq and single cell technologies) to characterise in detail those cells that contain latent HIV infection. Applying these techniques to individuals who stop antiretroviral therapy and are monitored longitudinally for viral rebound will allow further definition of the environment in which viral transcription is initiated.

The candidate will map the immune responses of individuals started on early antiretroviral therapy to determine how these are impacted by starting ART and which components of the immune response correlate with the reservoir and persisting viraemia. Additionally, samples from individuals under-going treatment interruption will allow further detailed  characterisation of immune correlation of rebound and remission.

The candidate will combine flow cytometry and molecular techniques to help clarify the phenotype of cells latently infected with HIV. Further objectives will explore changes in cell phenotype and gene expression profile that associate with rebound viraemia. Additionally, exploration of the antigen-specificity of latently infected cells through other approaches such as TCR sequencing and the ability to which these cells can be targeted by the immune system will be a parallel component of this project.

Training Opportunities

The candidate will be primarily supervised by Professor John Frater (Nuffield Dept of Medicine). The candidate will be expected to become proficient at flow cytometry and cell sorting (within a Category III Facility), as well as to develop molecular and analytic skills relevant to DNA amplification (PCR, qPCR) and gene expression studies. Full training will be provided in the laboratory and analytic skills required to undertake the DPhil. Over the course of the DPhil the candidate will be expected to contribute at lab meetings, journal clubs and other academic forums as well as to the overall duties of the research group.

Suitable candidates should have a good honours degree (1st Class or 2.1 minimum) in Biology, Immunology or Microbiology. A relevant Masters degree will be considered as an advantage. Candidates should have excellent written and oral communication skills. It would also be advantageous if they had previous experience of experimental research.

 

Further enquiries to: Suki Kenth; Email: suki.kenth@ndm.ox.ac.uk

Theme

Immunology & Infectious Disease and Tropical Medicine & Global Health

Admissions

Project reference number: 933

Funding and admissions information

Supervisors

Name Department Institution Country Email
Professor John Frater Experimental Medicine Division Oxford University, Peter Medawar Building GBR john.frater@ndm.ox.ac.uk
Professor Philip Goulder Department of Paediatrics University of Oxford GBR philip.goulder@paediatrics.ox.ac.uk

There are no publications listed for this DPhil project.