Understanding B cell development in immunity: age-related changes

The overall aim of the project will be to investigate how molecular pathways in antigen-induced B cell development differs with age.

Start date

1 October 2023

Duration

4 years

Application deadline

Funding source

Faculty of Health and Medical Sciences at the University of Surrey and Agency for Science, Technology and Research (A*STAR) in Singapore

Funding information

Whilst the candidate is in the UK, the University of Surrey funding will include UKRI-aligned stipend (£17,668 pa for 2022-23) and approved fees. Whilst in Singapore, funding from A*STAR will consist of a stipend (inclusive of housing subsidy) of SGD 3300/month, a one-time airfare grant to Singapore of SGD 1,500, a one-time settling-in allowance in Singapore of SGD 1,000, a one-time IT allowance of SGD 800, medical insurance and a conference allowance.

About

A healthy immune system has a good balance between making effective immune responses and avoiding autoimmune disease. Unfortunately, this balance is dysregulated with age. Older people are more prone to adverse consequences of infectious disease and cancer incidence increases with age. Autoimmune diseases such as Rheumatoid Arthritis and Giant Cell Arteritis are more common in older people.

Our research labs use a combination of wet lab methods and computational immunology to investigate the ageing of the immune system. The first two years will be based at the University of Surrey Immunology labs and the second two years will be based in A * Star Singapore Immunology Network (Jinmiao CHEN’s lab). 

The overall aim of the project will be to investigate how molecular pathways in antigen-induced B cell development differs with age. Identification of potentially important molecules will be carried out using data obtained from blood samples that were taken after vaccination with a COVID-19 vaccine.  Samples were taken every 2 days for a month and we have bulk Ig gene repertoire, and single cell transcriptomic data, from up to 10 volunteers. These molecules will be investigated during activation of primary cells in vitro, either as co-cultures or as 3D organoids. The effects of changing culture conditions will be monitored by traditional methods such as microscopy and FACS imaging, as well as by PCR analysis of switch circles to detect class switching of antibodies and also single cell transcriptomics and metabolomics. In particular, the cultures will be undertaken using primary cells from both younger and older people to identify any differences.

The in-house single-cell RNA-seq and BCR-seq data will be integrated with all publicly available single-cell data to construct human B cell transcriptome and repertoire atlases. The atlases will encompass different tissue types, healthy and diseased states, untreated and treated. Using available age information, genes associated with immuno-ageing will be identified for each tissue type to investigate tissue-specific B cell ageing patterns. With the identified ageing markers, machine learning models will be trained to predict the B cell age of individuals in healthy and diseased states. Furthermore, transcriptional changes and class switch associated with diseases or vaccinations will be identified by comparing against healthy samples and steady states. Findings from analysing single-cell data in Dr Jinmiao Chen’s lab at A * STAR Singapore will be experimentally validated in Prof Deborah Dunn-Walters’ lab at University of Surrey.

For further information please email Prof. Deborah Dunn-Walters (d.dunn-walters@surrey.ac.uk) and Prof. Jinmao Chen (Chen_Jinmiao@immunol.a-star.edu.sg).

Related links

Professor Jinmao Chen Professor Deborah Dunn-Walters

Eligibility criteria

Open to UK and international students with the project starting in October 2023.

You will need to meet the minimum entry requirements for our Biosciences and Medicine PhD programme.

How to apply

Applicants are strongly encouraged to contact the relevant principal supervisor(s) to discuss the project(s) before submitting their application.

Applications should be submitted via the Biosciences and Medicine PhD programme page (N.B. Please select the October 2023 start date when applying).

You may opt to apply for 1, 2 or all 3 of the studentship currently available projects via this joint programme.

When completing your application, in place of a research proposal, please provide a brief motivational document (1-page maximum) that specifies:

  • The reference numbers(s) for the project or projects you are applying for,
  • The project title(s) and principal supervisor name(s),
  • If applying for more than one of the projects, please also indicate your order of preference,
  • An explanation of your motivations for wanting to study for a PhD, and
  • An explanation of your reasons for selecting the project(s) you have chosen.

Additionally, to complete a full application, you MUST also email a copy of your CV and 1-page motivational document directly to the relevant project principal supervisor of each project you apply for. Due to short turnaround times for applicant shortlisting, failure to do this may mean that your application is not considered.

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