Using Mass Spectrometry to identify new antigens for TB vaccines

Project Overview

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a successful intracellular pathogen that resides and grows inside macrophages. Infected cells are known to present antigenic peptides through the MHC molecules. These peptides can be recognized by T-cells that mount an adaptive response against the pathogen. We want to explore this biologic process to develop a new generation of subunit TB vaccine candidates to boost the current BCG vaccine.

With the aim of discovering new and unexplored peptides presented by MHC Class I molecules in infected macrophages and dendritic cells with the virulent Mycobacterium tuberculosis, as well as non-virulent Mycobacterium bovis BCG, this project consists of the qualitative and quantitative analysis of peptides, by mass spectrometry. The functional activity of the newly identified peptides as well as of their precursor antigens will be assessed by in vivo and in vitro immunologic assays. The antigens will then be evaluated by generating recombinant viral vectors. The most promising antigens will be characterised and progressed towards early phase clinical trials.

This very exciting DPhil project is a multi-disciplinary study, including the highly sophisticated, state-of-the-art identification of peptides by mass spectrometry, proteomics, transcriptomics, immunology and molecular biology. This project combines the major steps for the development of a new generation of tuberculosis vaccines, through antigen identification, vaccine design, and pre-clinical validation.

Training Opportunities

Both subject specific and generic training in research skills will be provided. Specific training will be available in mass spectrometry, proteomics, transcriptomics, vector construction, molecular biology, immunization techniques, a large variety of immunoassays, microbiology, microscopy, statistical analysis of data and experimental design. The McShane research group is large and includes students, post-docs, clinical fellows, research nurses, project managers, thereby providing exposure to a broad range of research and development activities in the biomedical sciences. 

Theme

Immunology & Infectious Disease and Tropical Medicine & Global Health

Admissions

Project reference number: 716

Funding and admissions information

Supervisors

Name Department Institution Country Email
Professor Helen McShane Jenner Institute Oxford University, Old Road Campus Research Building GBR helen.mcshane@ndm.ox.ac.uk
Dr Paulo Bettencourt Jenner Institute University of Oxford GBR paulo.bettencourt@ndm.ox.ac.uk

There are no publications listed for this DPhil project.