Vaccine LEGACY – Applying a systems based approach to accelerate vaccine development

New technologies are transforming and accelerating both vaccine development but also the molecular and cellular mechanism regulating the efficacy of human immune responses to vaccines.  Systems based approaches can provided single cell resolution of immune dynamics in vivo.  In the LEGACY (Lymph node singe-cell Genomics AnCestrY) network program we used  in vivo human lymph node sampling using fine needle aspirate to analyse the dynamics immune responses acquiring both single cell gene expression, T cell and B cell receptor sequence and associated clinical measurement on lymph node swelling.  In this project the student will develop and apply machine learning to existing datasets from LEGACY and new studies on vaccines from emerging pathogens.  To date much of the focus of vaccines has been on protective humoral responses, however there is increasing evidence of the key role of CTLs in vaccine efficacy, thus we have developed a tool to predict antigenic epitopes, Predictors of Epitopes by Mechanism (POEM) in this project we will aim to combine POEM with DATA DECODER to analyse how vaccines to emerging pathogens could be improved through systems-based optimisation. This project will require some background experience in systems biology or computer science, engineering or similar computational experience.

KEYWORDS

Vaccines, Systems Biology, Human Immunology

TRAINING OPPORTUNITIES

This interdisciplinary project will provide key training opportunities in computational biology including python programming, single cell analysis techniques and machine learning working in the context of high dimensional datasets. Depending on interest training will be provide on sample processing on 10x and high content analysis techniques on patient samples. 

KEY PUBLICATIONS

COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium, A blood atlas of COVID-19 defines hallmarks of disease severity and specificity, Cell. 2022 Mar 3;185(5):916-938.e58. doi: 10.1016/j.cell.2022.01.012.

Curion F, Rich-Griffin C, Agarwal D, Ouologuem S, Rue-Albrecht K, May L, Garcia GEL, Heumos L, Thomas T, Lason W, Sims D, Theis FJ, Dendrou CA., Panpipes: a pipeline for multiomic single-cell and spatial transcriptomic data analysis.  Genome Biol. 2024 Jul 8;25(1):181. doi: 10.1186/s13059-024-03322-7.

Flaxman A, Sebastian S, Appelberg S, Cha KM, Ulaszewska M, Purushotham J, Gilbride C, Sharpe H, Spencer AJ, Bibi S, Wright D, Schmidt I, Dowall S, Easterbrook L, Findlay-Wilson S, Gilbert S, Mirazimi A, Lambe T.  Potent immunogenicity and protective efficacy of a multi-pathogen vaccination targeting Ebola, Sudan, Marburg and Lassa viruse.  PLoS Pathog. 2024 Jun 26;20(6):e1012262. doi: 10.1371/journal.ppat.1012262.

Day S, Kaur C, Cheeseman HM, de Groot E, McFarlane LR, Tanaka M, Coelho S, Cole T, Lemm NM, Lim A, Sanders RW, Asquith B, Shattock RJ, Pollock KM. Comparison of blood and lymph node cells after intramuscular injection with HIV envelope immunogens. Front Immunol. 2022 Oct 5;13:991509. doi: 10.3389/fimmu.2022.991509.

THEMES

Vaccines, Systems Biology, Immunology, Machine Learning

CONTACT INFORMATION OF ALL SUPERVISORS

mark.coles2@kennedy.ox.ac.uk

teresa.lambe@paediatrics.ox.ac.uk

katrina.pollock@paediatrics.ox.ac.uk

jacqueline.siu@kennedy.ox.ac.uk

calliope.dendrou@imm.ox.ac.uk

The Kennedy Institute is a proud supporter of the Academic Futures scholarship programme, designed to address under-representation and help improve equality, diversity and inclusion in our graduate student body.  The Kennedy and the wider University rely on bringing the very best minds from across the world together, whatever their race, gender, religion or background to create new ideas, insights and innovations to change the world for the better. Up to 50 full awards are available across the three programme streams, and you can find further information on each stream on their individual tabs (Academic futures | Graduate access | University of Oxford).

How to Apply

Please contact the relevant supervisor(s), to register your interest in the project, and the departmental Education Team (graduate.studies@ndorms.ox.ac.uk), who will be able to advise you of the essential requirements for the programme and provide further information on how to make an official application. 

Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable). The application guide and form is found online and the DPhil or MSc by research will commence in October 2025. 

Applications should be made to the following programme using the specified course code. 

D.Phil in Molecular and Cellular Medicine (course code: RD_MP1) 

For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.

Interviews to be held week commencing 13^th January 2025.