Investigating Matrix Degradation Products in Tuberculosis

研究结核病中的基质降解产物

• 批准号: MR/R001065/1
• 负责人: Hannah Schiff
• 金额: $ 36.14万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR001065%2F1
• 关键词: Investigating; Matrix; Degradation; Products; Tuberculosis

Tuberculosis is a lung infection that spreads by people coughing. It continues to cause disease worldwide, killing over 4,000 people per day, and is becoming progressively more resistant to the antibiotics used to treat it. New innovative approaches to control the disease are urgently needed as standard diagnosis and treatment have remained largely unchanged for the last 30 years. Tuberculosis causes very extensive damage to the lungs and we have shown that this releases small fragments of lung fibrils into the bloodstream. Lung destruction differs between men and women with tuberculosis, and also when tuberculosis occurs in the context of HIV infection. Professor Paul Elkington's research group has previously studied a small number of the fragments released by infection, but as the lung is a highly complex network of interconnected fibrils many fragments will be produced in tuberculosis. This project will measure the full range of fragments using a new type of analytical system called proteomics that can identify all the proteins in a single sample. These fragments can then be used to develop tests to identify patients who are coughing tuberculosis and actively infecting others, and also to monitor the effect of new treatments.I will analyse samples that have been collected as part of other studies and include the important groups for comparison: men and women, HIV uninfected and HIV infected individuals, and patients with other respiratory conditions who have symptoms suggestive of tuberculosis. First, I will measure all the matrix breakdown products in a small number of samples using a highly sensitive but time-intensive testing system comparing patients with active tuberculosis with healthy controls. Next, I will perform detailed computational analysis of all the fragments identified and how they differ between the groups. Once the most interesting fragments are identified, I will measure these using rapid, high-throughput approaches in a much larger number of samples, including individuals with other respiratory conditions that can mimic tuberculosis to characterise the diagnostic potential as a test to exclude tuberculosis. Finally, I will study these fragments in patients of different ethnic origin and various manifestations of tuberculosis. This study will perform the first systematic investigation of lung matrix degradation products in tuberculosis and I will identify fragments that can be used to develop a new diagnostic test to break the cycle of infection. The project will also provide me with an excellent training in cutting edge medical research methods that can be used to address a wide range of human diseases.

肺结核是一种通过咳嗽传播的肺部感染。它继续在世界范围内引发疾病，每天导致4000多人死亡，并对用于治疗它的抗生素产生越来越强的抗药性。迫切需要新的创新方法来控制这种疾病，因为标准的诊断和治疗在过去30年中基本上没有变化。肺结核会对肺部造成非常广泛的损害，我们已经证明，这会将肺纤维的小碎片释放到血液中。男性和女性结核病患者的肺部破坏不同，在艾滋病毒感染的背景下发生结核病时也是不同的。保罗·埃尔金顿教授的研究小组此前研究了感染释放的一小部分碎片，但由于肺是一个高度复杂的相互连接的纤维网络，因此在肺结核中会产生许多碎片。该项目将使用一种名为蛋白质组学的新型分析系统来测量所有片段，该系统可以识别单个样本中的所有蛋白质。然后，这些碎片可以用来开发测试，以确定哪些患者正在咳嗽并积极感染他人，也可以监测新治疗方法的效果。我将分析作为其他研究的一部分收集的样本，并包括用于比较的重要群体：男性和女性、未感染艾滋病毒和感染艾滋病毒的个人，以及具有结核病症状的其他呼吸道疾病患者。首先，我将使用一种高度敏感但耗时的测试系统来测量少量样本中的所有基质分解产物，将活动性结核病患者与健康对照组进行比较。接下来，我将对识别的所有片段以及它们在不同组之间的差异进行详细的计算分析。一旦确定了最有趣的片段，我将在更多的样本中使用快速、高通量的方法来测量这些片段，包括患有其他呼吸道疾病的人，这些人可以模仿结核病，以表征诊断潜力，将其作为排除结核病的测试。最后，我将研究这些片段在不同种族来源和不同表现的结核病患者中的表现。这项研究将对结核病中的肺基质降解产物进行首次系统研究，我将确定可用于开发一种新的诊断测试以打破感染循环的片段。该项目还将在尖端医学研究方法方面为我提供极好的培训，这些方法可用于解决广泛的人类疾病。