Bioengineering to combat the tuberculosis pandemic Infectious diseases remain an ongoing cause of poor health and mortality in the poorest countries in the world. Tuberculosis kills more humans than any other infection and is principally a disease of poverty. Unfortunately recent studies examining new vaccine approaches or shorter antibiotic courses have not been successful, demonstrating that more research and understanding of the disease is required to combat the pandemic. Tuberculosis is also becoming progressively more resistant to antibiotics used to treat it. It is widely accepted that highly innovative approaches that draw on diverse specialists are required to achieve control of tuberculosis.  This project will combine expertise at the University of Southampton, which specifically focuses on cross-disciplinary research, with the African Health Research Institute in Durban, a state-of-the-art laboratory set up to be at the heart of the tuberculosis and HIV pandemics. It is centred on a new way of studying infection in the laboratory, which relies on an innovative cellular spraying technique that permits studies of infected human cells in three-dimensions and attached to lung supporting fibres. This system has been developed at Southampton and will be introduced laboratories in Durban, where we will harness the expertise in investigation of samples from patients and fluidics to further develop the model. We will prove that this system can be used to understand how infection occurs, to investigate new vaccine strategies and to identify novel antibiotic regimes.  There will be four programmes of work which will take place both in Southampton and Durban, with regular exchange of researchers between the centres, joint conferences and scheduled videoconferences. First, we will study cells isolated from lungs removed during surgery as part of their routine clinical care.  We will compare cells from patients who either are controlling tuberculosis infection or who have developed disease to examine the factors leading to active disease. Secondly, we will separate cells which are controlling infection from cells where infection is progressing and systematically study biology to understand how human cells either control infection or permit progression. Thirdly, we will change the host immune cells using genetic engineering technology to unpick which components of the body's immune response is beneficial in controlling infection compared to that which causes damage. Finally, we will combine the human cell system with miniature fluid irrigation apparatus to permit modulation of antibiotic concentrations over time to identify l more effective treatment regimes.  This project will deliver a transformative approach to the tuberculosis pandemic, identifying new vaccine targets and antibiotic regimes, and initiate a highly complimentary collaboration which we will develop over the two years to deliver innovative cross-disciplinary research to address diseases affecting the poorest in the world. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.