Microbial community ecology of chronic respiratory infections

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?