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的持续原因。结核病比任何其他感染导致的死亡人数都要多，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缩短抗生素疗程的研究没有取得成功，这表明需要对该疾病进行更多的研究和了解，以抗击大流行。结核病对用来治疗它的抗生素也变得越来越耐药。人们普遍认为，需要高度创新的方法，利用不同的专家来实现结核病的控制。该项目将结合南安普顿大学专门从事跨学科研究的专业知识，以及德班的非洲卫生研究所，这是一个处于结核病和艾滋病毒大流行核心的最先进的实验室。它的核心是一种在实验室研究感染的新方法，该方法依赖于一种创新的细胞喷洒技术，该技术可以对受感染的人体细胞进行三维研究，并附着在肺支持纤维上。该系统已在南安普敦开发，并将引入德班的实验室，我们将在那里利用从患者和流行性疾病样本调查方面的专业知识来进一步开发该模型。我们将证明，这一系统可用于了解感染是如何发生的，研究新的疫苗策略和确定新的抗生素方案。将有四个工作方案在南安普敦和德班举行，中心之间将定期交换研究人员，联合会议和预定的视频会议。首先，作为常规临床护理的一部分，我们将研究从手术中取出的肺中分离出的细胞。我们将比较正在控制结核病感染或已发展为疾病的患者的细胞，以检查导致活动性疾病的因素。其次，我们将从感染进展的细胞中分离出控制感染的细胞，并系统地研究生物学，以了解人类细胞是如何控制感染或允许进展的。第三，我们将使用基因工程技术改变宿主免疫细胞，以找出与造成损害相比，身体免疫反应中哪些成分对控制感染有利。最后，我们将把人体细胞系统与微型液体灌溉设备结合起来，允许随着时间的推移调节抗生素浓度，以确定L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的方法，确定新的疫苗目标和抗生素方案，并启动高度赞扬的合作，我们将在两年内发展这种合作，提供创新的跨学科研究，以解决影响世界上最贫穷人口的疾病。

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.