{"id":"https://openalex.org/G6013166300","display_name":"Learning from the thymic human cell atlas for T cell engineering","description":"One of the central questions in immunology is how adaptive immunity generates its diversity while maintaining tolerance. The key\nmediators of tolerance are T cells, which develop in the thymus, where thymocytes rearrange their T cell receptor genes and undergo\npositive and negative selection. This ensures their ability to recognise antigen in the context of MHC, whilst avoiding self-reactivity.\nWe are still far from fully understanding the steps in these processes at the molecular level, especially in humans: What are the\ndevelopmental trajectories of different T cell subtypes, and how do they relate to their journey through the organ during maturation?\nWhat is the functional role played by the macro- and micro-scale environments in regulating this? These questions have gained in\nimportance since several T cell types are now therapeutics in cancer and transplantation, raising the question of how to engineer\nspecific T cell subsets in vitro.\nIn AIM 1, we propose to generate an organ-scale 3D thymic cell atlas at full genomic breadth through genomics and imaging\ntechnologies. By combining multi-modal single cell genomics with multi-scale spatial genomics and imaging technologies, we will\ngenerate a rich data set for deep and comprehensive reconstruction of tissue architectures in a thymic lobe.\nIn AIM 2, we will carry out computational data integration with new methods for 3D multi-modal atlas assembly to predict\nlymphocyte developmental mechanisms at micro and macro scales.\nIn AIM 3, we will use an artificial thymic organoid system to simultaneously validate our findings and enhance T cell engineering\napproaches.\nThis powerful integrated approach combines genomics, imaging and tissue engineering together with computational analyses to\ndissect design principles of the thymus, a central organ of the immune system. This knowledge will guide the development of\nengineered T cells as research reagents, and ultimately as therapeutics.","funder_award_id":"EP/Y02978X/1","funder":{"id":"https://openalex.org/F4320334627","display_name":"Engineering and Physical Sciences Research Council","doi":"10.13039/501100000266"},"funded_outputs":["https://openalex.org/W4402348973"],"funded_outputs_count":1,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":2117319.0,"currency":"GBP","amount_usd":2594424.75,"amount_usd_basis":"daily_rate","recipients":[{"id":"https://openalex.org/I2802476451","display_name":"Wellcome Sanger Institute","ror":"https://ror.org/05cy4wa09","country_code":"GB","roles":["lead"],"share":null,"basis":"affiliation_matcher","asserted_by":"funder"}],"recipient_countries":[{"country_code":"GB","share":1.0,"amount_usd":2594424.75,"basis":"organisation_location"}],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"Horizon Europe Guarantee","start_date":"2023-09-30","end_date":"2024-04-13","start_year":2023,"end_year":2024,"landing_page_url":"https://gtr.ukri.org/projects?ref=EP/Y02978X/1","doi":null,"provenance":"gateway_to_research","lead_investigator":null,"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G6013166300","primary_topic":{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.8134,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.8134,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"institution_awarded":[],"updated_date":"2026-10-17T03:01:12.000Z","created_date":"2026-07-13T04:25:00.000Z"}