Understanding B cell development in immunity: age-related changes

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).

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.