Project ID CM-HD2024_38


Co Supervisor 1A Faculty of Life Sciences & Medicine, School of Life Course & Population Sciences, Department of Twin Research & Genetic EpidemiologyWebsite

Co Supervisor 1B Faculty of Life Sciences & Medicine, School of Life Course & Population Sciences, Department of Twin Research & Genetic EpidemiologyWebsite

Unravel the link between immunosenescence and inflammation through systems immunology approaches

While lifespan is increasing across the globe, healthy, disability-free life expectancy in older age is highly variable. Ageing is accompanied by immunosenescence and chronic inflammation, both associated with increased frailty and incidence of common age-related diseases including cancer, and autoimmune, metabolic, and cardiovascular diseases. There is currently limited understanding of which core of immune cells, when disrupted, drive this process.

This research project will exploit a unique dataset generated in the TwinsUK cohort including:
a) a high-resolution snapshot of the immune system, comprising 90,000 immune variables, detailing both cell types and cell-surface protein expression (immunophenotypes),
b) multiple molecular markers of biological vs chronological age, and a panel of 92 proteins associated with inflammatory diseases and related biological processes
c) multi-omics data already generated in TwinsUK, including genomics, glycomics, metabolomics, metagenomics, and lifestyle and diet data.

The researcher will use systems immunology approaches to identify clusters (modules) of immune cells that associate with ageing. The relationships between these modules of immune cells and inflammatory proteins will be investigated to gain deeper insights into the connection between immunosenescence, inflammation, and the aging process.
Integration of multi-omics and lifestyle/diet data will identify easily accessible biomarkers for the identification of early hallmarks of immunosenescence, as well as targets for prevention and intervention.
The student will develop solid computational and data analysis skills, and learn how to successfully manipulate and analyse large biomedical datasets.

Representative Publications

Suhre, K., Trbojević-Akmačić, I., Ugrina, I., Mook-Kanamori, D. O., Spector, T., Graumann J, Lauc H, Falchi M., Fine-Mapping of the Human Blood Plasma N-Glycome onto Its Proteome, MDPI Metabolutes, 2019, DOI: 10.3390/metabo9070122; Visconti A.†, Le Roy C.I.†, Rosa F., Rossi N., Martin T.C., Mohney R.P., Li W., de Rinaldis E., Bell J.T., Venter J.C., Nelson K.E., Spector T.D.‡, and Falchi M.‡, Interplay between the human gut microbiome and host metabolism, Nature Communications, 2019, doi:10.1038/s41467-019-12476-z; Visconti A., Martin T.C., and Falchi M., YAMP: a containerised workflow enabling reproducibility in metagenomics research, GigaScience, 2018, doi:10.1093/gigascience/giy072
Zhang X., Adebayo A.S., Wang D., Raza Y., Tomlinson M., Dooley H., Bowyer R.C.E., Small K., Steves C.J., Spector T.D., Duncan E.L., Visconti A.‡, and Falchi M.‡, PPI-induced changes in plasma metabolite levels influence total hip bone mineral density in a UK cohort, Journal of Bone and Mineral Research, 2022 doi:10.1002/jbmr.4754; Piaggeschi G., Rolla S., Rossi N., Brusa D., Naccarati A., Couvreur S., Spector T.D., Roederer M., Mangino M., Cordero F., Falchi M.‡, and Visconti A.‡, Immune trait shifts in association with tobacco smoking: a study in healthy women, Frontiers in immunology, 2021, doi:10.3389/fimmu.2021.637974; Visconti A., Rossi N., Deriš H., Lee K.A., …, Sasieni P., Bataille V.‡, Lauc G.‡, and Falchi M.‡, Total serum N‐glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma, BMC Cancer, 2023 doi:10.1186/s12885-023-10511-3