This project uses high-performance computing to investigate how innate and adaptive lymphocytes regulate tissue immunity in the human gastrointestinal tract, with a particular focus on inflammatory bowel disease (IBD). NAISS resources enable the integration and analysis of large multimodal single-cell datasets, including transcriptomic, surface-protein, spatial, and immune-receptor information. The first phase of the project defined a conserved molecular programme through which type 3 innate lymphoid cells (ILC3s) activate latent TGF-β1 in healthy and inflamed intestinal tissue. This work resulted in the article “ILC3s mediate intestinal immune-epithelial interactions via TGF-β1 activation,” published in Mucosal Immunology in 2025. Project resources also supported analyses contributing to an article on immature innate lymphoid cells in colorectal cancer, published in Nature Communications in 2026. Our current principal focus is a multimodal single-cell analysis of more than 100,000 immune cells from colonic tissue. We are investigating how innate and adaptive lymphocytes are organized across the intraepithelial, mucosal, and submucosal layers and how this organization is disrupted in Crohn’s disease. Current work combines cell-state annotation, tissue-layer assignment, neighbourhood-based differential-abundance testing, and differential-expression analysis. These analyses form the basis of a manuscript provisionally titled “Spatial disorganization of innate and adaptive lymphocytes in colonic tissue layers in Crohn’s disease,” which is being prepared for submission before the end of 2026. Following completion of this work, we plan to continue analysis of a longitudinal cohort of patients with Crohn’s disease undergoing anti-TNF treatment. We will investigate changes in T-cell infiltration, clonality, and phenotype in responders and non-responders. NAISS resources remain essential for completing these analyses and directly support John Bassett’s doctoral research, forthcoming manuscript, and PhD thesis and defence scheduled for February 2027.