Microbial community ecology of chronic respiratory infections

世界卫生组织已将呼吸道疾病确定为全球人类发病和死亡的主要原因之一。在生态框架内，该CASE学生将专注于囊性纤维化（CF）患者肺部微生物感染的社区生态；CF患者的发病率和死亡率主要是由慢性微生物感染和伴随的气道炎症引起的。CF是慢性呼吸道感染的理想范例，因为它是一种定义明确的疾病，通常比其他呼吸道疾病肺功能下降（由于感染）更快。临床标本的微生物学分析传统上依赖于鉴定前的培养依赖方法，研究只关注少数目标细菌病原物种，包括；铜绿假单胞菌，金黄色葡萄球菌，流感嗜血杆菌和洋葱伯克氏菌复合物（BCC）。分子生物学方法在环境微生物学中得到了发展和广泛应用，有望为以前被认为具有良好特征的感染提供新的见解。例如，最近基于分子生物学的研究表明，CF痰中的细菌多样性水平远高于之前所接受的水平。虽然已知的病原体显然很重要，但直到现在人们才认识到，慢性定植的CF气道代表了一个令人惊讶的复杂和多样化的生态系统，从群落生态学的角度理解CF肺可能有助于我们理解疾病进展并影响治疗方案。在这里，博士生将接受生态建模和统计、分子微生物生态学、临床微生物学和最新的前沿基因组测序技术方面的培训。这种创新的跨学科培训将使学生对CF微生物学的理解达到一个全新的水平，并解决以下基本问题：(1)在临床稳定的患者中，细菌分类群的多样性、丰度和分布是什么？(2)当患者发生肺加重时，这些社区特征是如何比较和对比的？(3)不同CF卓越中心CF患者群体的细菌群落生态是否存在区域差异？(4)古生菌和真核生物是否也在肺部疾病加重中发挥作用？

The World Health Organisation has identified respiratory illness as one of the leading global causes of human morbidity and mortality. Set within an ecological framework, this CASE studentship will focus on the community ecology of microbial infections within the lungs of cystic fibrosis (CF) patients; where morbidity and mortality in CF patients is primarily caused by chronic microbial infections and concomitant airway inflammation. CF makes an ideal paradigm for chronic respiratory infections as it is a well defined disorder and typically has a more rapid decline in lung function (due to infection) than other respiratory illnesses. The microbiological analysis of clinical specimens has relied traditionally upon culture dependent methods prior to identification and research has focused upon only a few targeted bacterial pathogenic species including; Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Burkholderia cepacia complex (BCC). The use of molecular biological approaches, developed and widely used in environmental microbiology, promise to provide fresh insights into infections that have previously been considered well characterised. For example, recent molecular biological based studies have shown that the level of bacterial diversity in CF sputum was much higher than previously accepted. Although known pathogens clearly are important, it is only now being recognised that chronically colonized CF airways represent a surprisingly complex and diverse ecosystem and understanding the CF lung in terms of its community ecology could benefit our understanding of disease progression and influence treatment regimens. Here the PhD student will be provided with training in ecological modelling and statistics, molecular microbial ecology, clinical microbiology, and the latest cutting edge genomic sequencing techniques. This innovative inter-disciplinary training will allow the student to gain an entirely new level of understanding in CF microbiology and to address the following fundamental questions: (1) What are the diversity, abundance and distribution of bacterial taxa across clinically stable patients? (2) How do those community characteristics compare and contrast when patients suffer pulmonary exacerbations? (3) Are there regional differences in the bacterial community ecology for groups of CF patients attending different centres for CF excellence? (4) Do archaeal and eukaryotic organisms also have a role to play in disease in pulmonary exacerbations?