T cell dysfunction is both a consequence of T cell ageing and drives multiorgan ageing1, which reframes immunosenescence as a metabolic disease.
The metabolic determinants of T cell ageing extend to the extracellular environment, where lipids are active instructors of immune cell fate across both innate and adaptive arms of immunity. For T cells specifically, extrinsic lipid regulation demonstrates that chylomicrons in circulating blood are taken up by naive CD8+ T cells via LDLR, delivering cholesterol to the lysosomal compartment where it activates mTORC1, driving translational priming of mitochondrial and effector programmes that persist durably through activation and expansion. Notably T cells have greater effector function when they are primed postprandially2.
Our lab investigates how organ-specific lipid milieus impact cancer invasion, organ tropism and immunity3-5, and the lipid species and ratios that organise the plasma membrane into functional nanodomains to control receptor clustering and modulate signalling thresholds across immune lineages. We want to study how ageing modifies the lipid composition of the extracellular milieu and how this impacts immune competence.
We will map how ageing sculpts the systemic and organ lipidome using lipidomics, lipoprotein fractionation, spatial approaches including superresolution microscopy across tissues (co-supervision: Dr Jonathan Worboys, Lydia Becker Institute, University of Manchester). We will focus particularly on lipid species and classes known to determine T cell activation quality. Beyond T cells, we will interrogate how the aged lipid environment shapes innate and adaptive immunity more broadly and contributes to tumour immunosurveillance. We will use in vivo approaches to modify the lipidome and test restoration of immune competence in antitumour immunity.
Main Supervisor: Amaya Virós
Co-Supervisor: Jonathan Worboys
Research Group: Skin Cancer and Ageing
University of Manchester entry: September 2027
References
- Desdín-Micó G, …Mittelbrunn M. T cells with dysfunctional mitochondria induce multimorbidity and premature senescence. Science. 2020 Jun 19;368(6497):1371-1376.
- Kumar A, … Delgoffe GM. Postprandial lipid metabolism durably enhances T cell immunity. Nature. 2026 Jun;654(8120):1065-1075.
- Gurung S, … Virós A. Stromal lipid species dictate melanoma metastasis and tropism. Cancer Cell. 2025 Jun 9;43(6):1108-1124.e11.
- Budden T, … Virós A. Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion. Nat Metab. 2026 May;8(5):1149-1172.
- Russell C, … Virós A. Brain lipid age governs melanoma metastatic growth and immune failure. Under review.
