Lymph nodE single cell Genomics AnCestrY immunity, infection, inflammation and immunisation (LEGACY IIII) Network

Context Lymph nodes are small bean shaped organs present in their hundreds throughout the body. They have important functions in protecting against infection, cancer and autoimmune diseases like rheumatoid arthritis. Many diseases and infections are associated with problems with lymph node function. Lymph nodes respond to vaccines by swelling beyond their normal size with white blood cells that make antibodies and that protect from infection. As well as vaccines, lymph nodes could be an important target for new drugs. Challenge the project addresses Despite their role in the body’s defence system, little is known about how lymph nodes work. Much of our current understanding comes from trying to estimate how they work by studying the blood or from studying them when they are diseased with cancer. This makes the process of discovering and testing new drugs and vaccines that work in lymph nodes challenging. At the University of Oxford and Imperial College London, we have recently developed a way of safely studying how lymph nodes work. Volunteers have an immunisation and donate lymph node cells by a procedure called fine needle aspiration (FNA). Ultrasound (US) is used to locate the lymph nodes and then a small amount of fluid and cells are taken alongside a blood test. The cells are studied in detail, to understand how they are working. At the University of Newcastle, a trial to give white blood cells directly into lymph nodes to treat rheumatoid arthritis is underway. There are centres across the UK that wish to develop lymph node research to answer important scientific questions, however, setting up and delivering it is highly specialist, requires a multi-disciplinary team and uses skills in imaging and data science that are rarely available for this kind of work. The Lymph nodE single cell Genomics AnCestrY immunity, infection, inflammation and immunisation (LEGACY IIII) Network is seeking to change this. Aims and objectives The LEGACY IIII Network will develop written, on-line and face-to-face training and research resources that will establish ten specialist centres across the UK. The Network will manage the data and support the establishment of infrastructure. We will develop new ways of working with lymph nodes to study cells and tissue biopsies at the single cell level. Training and development at these centres will be across two areas in human lymph node research: Research design and participant facing delivery Lymph node cell handling such as preservation and experimentation, and specialist data analysis Potential applications and benefits A national network of centres expert in lymph node research would be transformative for British science and would position the UK ahead of the global curve in this growing field. Centres face a significant clinical research skills gap and without support, this research is unlikely to grow meaningfully or to establish new techniques in lymph node research. The LEGACY IIII Network would overcome this with training and strategic regional development to circumvent current bottlenecks. In so doing, there will be multiple beneficiaries nationally and globally, in discovery science in infection and immunity, in drug and vaccine development, in commercial partnership and in aligned fields such as cancer research. With its cross-cutting multidisciplinary skillset housed within the LEGACY IIII Network centres, the UK will emerge as a leader in this exciting new field of research.