Bioengineering to combat the tuberculosis pandemic

传染病仍然是世界上最贫穷国家健康状况不佳和死亡率高的一个持续原因。结核病比任何其他传染病造成的死亡人数都多，它主要是一种贫困疾病。不幸的是，最近研究新的疫苗方法或更短的抗生素疗程的研究并不成功，这表明需要对这种疾病进行更多的研究和了解，以对抗这种流行病。结核病对用来治疗结核病的抗生素的抗药性也越来越强，人们普遍认为，要实现结核病的控制，就必须采用高度创新的方法，吸收不同的专家，该项目将把南安普顿大学专门侧重于跨学科研究的专门知识与德班的非洲卫生研究所结合起来，这是一个最先进的实验室，位于结核病和艾滋病流行病的中心。它的核心是在实验室中研究感染的新方法，该方法依赖于一种创新的细胞喷雾技术，该技术允许在三维空间中研究受感染的人体细胞并附着在肺部支持纤维上。该系统已在南安普顿开发，并将引入德班的实验室，在那里我们将利用患者样本调查和射流技术的专业知识进一步开发该模型。我们将证明，这一系统可用于了解感染是如何发生的，调查新的疫苗战略和确定新的抗生素方案。将有四个工作方案将在南安普顿和德班进行，各中心之间定期交换研究人员，举行联合会议和预定的电视会议。首先，我们将研究从手术中取出的肺中分离的细胞，作为其常规临床护理的一部分。我们将比较来自正在控制结核感染或已发生疾病的患者的细胞，以检查导致活动性疾病的因素。其次，我们将把控制感染的细胞与感染进展的细胞分开，并系统地研究生物学，以了解人类细胞如何控制感染或允许感染进展。第三，我们将利用基因工程技术改变宿主的免疫细胞，以挑选出与造成损害的免疫反应相比，身体免疫反应中哪些成分有利于控制感染。最后，我们将联合收割机与微型流体冲洗装置相结合，以允许随着时间的推移调节抗生素浓度，从而确定更有效的治疗方案。该项目将为结核病大流行提供一种变革性方法，确定新的疫苗靶点和抗生素方案，并启动一个高度互补的合作，我们将在两年内发展，以提供创新的跨-学科研究，以解决影响世界上最贫穷者的疾病。

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.