Cystic fibrosis and COPD are debilitating, life-threatening diseases characterised by airway inflammation, oxidative stress, persistent airway exacerbations and abnormal lung microbiome. CF is the most common lethal genetic disorder in Caucasians, affecting ≥3,500 people in Australia and NZ and more than 70,000 globally. It affects the lungs, gastrointestinal tract, liver and pancreas. CF is caused by mutations in the CFTR gene, encoding a cell membrane chloride channel. Most of the morbidity and mortality relates to airway infection beginning in early infancy and death usually occurs from lung sepsis by the fourth decade. The lung microbiome in CF is complex, but in most patients P. aeruginosa becomes the dominant pathogen and once established in antibiotic resistant biofilms, it is very difficult to eradicate with existing strategies. Strong circumstantial evidence exists that iron regulation in the CF lung is abnormal and that this promotes bacterial infection, especially with biofilm forming P. aeruginosa.
COPD currently affects about 200 million people globally and in most cases is caused by cigarette smoke. COPD is characterised by increased airway inflammation and mucous (bronchitis) and non-reversible destruction and enlargement of the air spaces (emphysema). There are many similarities in the lung phenotype between CF and COPD, and interestingly, increased iron has been shown in the lungs of both CF and COPD patients.
- Establish in vitro models of cigarette-smoke exposure of healthy and disease epithelial cells.
a. Subsequently, incorporate Pseudomonas bacteria in co-culture experiments.
- Characterise lung iron homeostasis in CF and COPD, using in vivo (CFTR knockout mouse) and in vitro.
- Investigate if synthetic iron chelators can eradicate Pseudomonas infection, using in vitro and in vivo.
This project is suitable for an Honours student only. We are looking for an enthusiastic, hard-working student, who has some basic background in human biology, immunology and microbiology. The student will gain skills in mouse handling, breeding and genotyping of knockout mice; as well as techniques such as RNA extraction, quantitative PCR, western blotting and also skills in cell culture using CF, COPD and healthy cell lines.
Dr Pramila Maniam
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