Lung function and damage over the life course and the effects of chemical agents

肺是人体的重要组成部分，负责氧气和二氧化碳的气体交换。肺本身是复杂的，由许多不同的区域组成，这取决于功能和细胞类型。在一个人的一生中，他们的肺部会受到一系列感染和环境污染物的影响，在冲突期间还会受到蓖麻毒素和氯气等化学制剂的潜在使用。肺里有一种特殊的细胞，可以提供第一道防御传染病和化学物质的屏障。然而，这种创伤可导致气道重塑现象，并在极端情况下导致死亡或表现为终身呼吸困难。利用国防科学技术实验室的专业设施，我们对遭受化学损伤的肺组织进行了广泛的转录组学（mrna）和蛋白质组学（蛋白质）分析。成千上万的分子被鉴定和量化，以及详细的临床信息。这些数据集是随着时间的推移而收集的，为了解肺损伤的影响和后果提供了前所未有的窗口。博士项目将使用信息学来整合这些数据（转录组学/蛋白质组学/临床参数），以提供肺损伤的计算机模型。这将集中在差异基因表达分析，以确定修改的信号通路和潜在的途径，可以治疗的目标。具体突出的途径将进一步研究使用离体肺模型。因此，该项目将涉及计算生物学和湿生物学。该项目将以利物浦大学为基地，包括对位于Porton Down的国防科学技术实验室进行短期研究访问。

Lungs are an essential component of humans and are responsible for the gaseous exchange of oxygen and carbon dioxide. The lung itself is complex and is composed of many different regions, depending on function, and cell types. Over the life course of a person, their lungs are subjected to a range of infections and environmental pollutants, and during conflict the potential use of chemical agents such as ricin and chlorine gas. Special cells in the lung are present that can provide a first defence against infectious and chemical agents. However, such traumas can result in the phenomenon of airway remodelling and result in extreme cases in death or present as lifelong breathing difficulties. Using specialist facilities at the Defence Science Technology Laboratory we have extensive transcriptomic (mRNAs) and proteomic analysis (proteins) of lung tissue subjected to chemical damage. Many thousands of molecules were identified and quantified, as well as detailed clinical information. These datasets were gathered over time and represent an unprecedented window into the effects and consequences of lung damage. The PhD project will use informatics to integrate this data (transcriptomics/proteomics/clinical parameters) to provide an in-silico model of lung damage. This will focus on differential gene expression analysis to identify modified signalling pathways and potential pathways that can be therapeutically targeted. Specific highlighted pathways will be further investigated using ex vivo models of the lung. Thus, the project will involve both computational and wet biology. The project will be based at the University of Liverpool and involve short term research visits to the Defence Science Technology Laboratory located at Porton Down.