Honours & Masters (M.Sc) Projects
1. Defining the virulence mechanisms of antibiotic resistant Klebsiella pneumoniae
Klebsiella pneumoniae is one of the World Health Organization's (WHO) highest priority bacterial pathogens for development of new therapeutic solutions. This is due to the lack of a vaccine against K. pneumoniae and the high-level resistance of the pathogen to current antibiotics and in-development novel antibiotics. Critical to the development of alternative treatment strategies is understanding how it mediates disease in humans. However, despite the importance of K. pneumoniae, there remains many gaps in our knowledge regarding its fundamental biology and virulence mechanisms. This project will focus on characterising newly discovered pathways that enable this pathogen to overcome the innate immune response of the host using a combination of genomic, molecular microbiological, and biochemical techniques. By understanding these pathways, it will be possible to develop new therapeutic strategies that target these host evasion mechanisms.
2. Zinc homeostasis in Pseudomonas aeruginosa
Pseudomonas aeruginosa is a major opportunistic human pathogen and the leading cause of death in cystic fibrosis. During infection, the essential micronutrient zinc is withheld from invading pathogens by the host immune response. Our recent studies have now identified some the mechanisms that P. aeruginosa uses to compete zinc away from the host in the lung environment, thereby facilitating pathogen survival. This project will use our detailed insights to assess the roles of these major, yet uncharacterised, proteins and how they influence the growth and behaviour of P. aeruginosa. This study will use a combination of microbiology, molecular biology, and biochemistry to define the poorly understood pathways used in Gram-negative bacteria for zinc uptake.
3. Developing a novel therapeutic approach to treat Streptococcus pneumoniae infections
Streptococcus pneumoniae is one of the world’s foremost bacterial pathogens, responsible for more than one million deaths every year. Although we have antimicrobial treatments to control S. pneumoniae infections, rates of vaccine escape have been increasing over the past two decades as have resistance rates to frontline antibiotics. During infection, S. pneumoniae is exposed to high concentrations of the antimicrobial metal ion copper as part of the innate immune response. Although copper ions are directed against the pathogen to kill it, S. pneumoniae appears to have evolved elegant defence mechanisms that enable it to survive copper exposure and enhance its ability to cause host tissue damage and disease. This project will determine how S. pneumoniae subverts host antimicrobial copper and evaluate novel antimicrobials that target these resistance mechanisms.
4. Breaking bacterial antibiotic resistance using ionobiotics
Antibiotic-resistant bacterial pathogens represent an imminent global threat to human health in the 21st century. Rising rates of bacterial resistance and a waning pipeline for new antibiotic discovery and development requires new approaches to address this healthcare crisis. This project will investigate the use of novel metal ion shuttling compounds, which we have called ionobiotics, that break drug resistance in high priority bacterial pathogens and render them susceptible to antibiotic treatment. This approach has the potential to restore the efficacy of our existing antibiotic arsenal. This project will contribute to showing the range of antibiotics that can be rescued by ionobiotic treatment and define the mechanism of action using a combination of molecular, biochemical, and multi-omic approaches.