Mitochondrial Genome Stability and DNA repair
Genome Engineering technologies rely on robust and predictable responses to altered or damaged DNA bases. Limited understanding of mitochondrial DNA repair has hampered the development of technologies to reliably engineer the mitochondrial DNA (mtDNA) – a 16.5Kb circularized DNA fragment containing 37 genes critical for mitochondrial and associated cellular functions. In addition, each cell contains hundreds to thousands of copies of the mitochondrial genome – further compounding this challenge. In contrast to the nuclear genome, it remains unclear which DNA repair mechanisms operate in mitochondria. This project aims to elucidate the mechanisms that protect and repair mitochondrial DNA.
Investigating the Mitotoxicity of Fluoroquinolones
Antibiotics are the most fundamental tools we have in the fight against bacterial infections. Without these drugs, bacterial infections that could otherwise be easily treatable could become life-threatening, as such it has become paramount to ensure that these drugs can continue to be used and remain effective. However, a group of these antibiotics, known as fluoroquinolones, have been shown to cause number of severe and potentially permanent disabling side-effects in a proportion of the people who are prescribed them. This has resulted in the use of these highly-effective antibiotics being limited due to potential side-effects. Further research has demonstrated that the side-effects of fluoroquinolones result from defects in mitochondria in some patients, though it is unclear why some individuals suffer these side effects while others do not. This research aims to uncover the molecular basis of these severe adverse reactions.
Investigating the antimicrobial activity of hydroquinine
Hydroquinine, a cinchona alkaloid, has been shown to exhibit antimicrobial activity against a range of microorganisms including drug-sensitive and multidrug-resistant strains of Pseudomonas aeruginosa. In collaboration with Naresuan University (Thailand), we aim to characterise the molecular mechanism by which hydroquinine elicits its activity and examine whether the compound exhibits cellular toxicity at the doses required.
