Cambridge Centre for Research Assistant or Research Associate (Fixed Term)
Department of Medicine, Cambridge
Applications are invited to recruit an enthusiastic Research Assistant or Research Associate to work on an MRC-funded project with Professor Eoin McKinney in the Cambridge Institute for Immunotherapy and Infectious Disease (CITIID). Research within the McKinney group, funded by MRC and NIH grant support, is focused on integrating multimodal genomic data from human cohorts to gain insight into the aetiology underlying immune-mediated diseases, ranging from T1D and lupus through to vaccine responses and healthy ageing (see Xhonneux et al Sci Transl Med 2021, Fabre et al Nature 2022, Imrie et al Plos Digital Health 2023, Bashford-Rogers et al, Nature, 2019; McKinney et al, Nature, 2015;). The post will be based in Eoin McKinney's laboratory in the Jeffrey Cheah Biomedical Centre, incorporating CIITID and the Cambridge Stem Cell institute, on the Cambridge Biomedical Campus. The project also involves collaborations with groups in the Stem Cell Institute (Cambridge), Babraham Institute and in the CNR in Sardinia, Italy. Together, the team incorporates clinician scientists and academics with extensive expertise in multimodal integrated analysis.
We are interested in dynamic changes occurring within the immune system during ageing. Paradoxically, immune ageing sees features of relative immune deficiency (increased susceptibility to infection, reduced responses to vaccination) alongside immune dysfunction (increased inflammation and tendency toward autoimmunity). The mechanisms responsible and how age-related immune deficiency relates to age-related autoreactivity have remained obscure.
We have identified a novel pattern of altered immunity that accelerates in a non-linear fashion beyond 70 years of age and is associated with subsequent mortality risk. This pattern was identified through integration of multiple genomic datasets on a common set of over 5000 individuals, including quantification of autoantibodies, pathogen seroreactivity, serum proteomics, detailed flow cytometric immunophenotyping and antigen receptor sequencing for both B and T cell populations. This has allowed us to define an individual's 'immune age' as variance relative to the expected age-related distribution. Individuals with either too much or too little age-related change show worse outcome with evidence of autoimmunity accompanying maintained productive responses.
The project will use an established protocol for pre-enriching peripheral immune cell populations from blood taken during an experimental medicine study of vaccination in a healthy, aged individuals. Samples will be characterized using multi-omic single cell analysis. Integrative analyses will combine high-throughput datasets, including single cell RNA-sequencing, multi-parameter spectral flow phenotyping and antigen receptor repertoire analysis alongside clinical meta-data. The goal will be to identify mechanisms of altered immune responsiveness in age and, ultimately, how they might be modulated. In doing this they will enhance their analytic skills, but also become familiar with both immunology and experimental medicine.