Research

Paul Harris

Synthetic peptides as next generation antibiotics

Peptides, long chains of amino acids, are used as antibiotics and due to their unique mode of action, resistance by bacteria is difficult.  FDA approved Daptomycin and Colistin are current last line defence antibiotics, nonetheless resistance and toxicity are developing issues. We undertake chemical synthesis of known antibacterial peptides and then use different chemistries to improve their effectiveness while decreasing any side effects. We also tackle the total chemical synthesis of any newly discovered antibacterial peptides to confirm their structure and activity and then undertake a medicinal chemistry program, to probe how modifications of the compound effect their antibacterial properties.

Ghader Bashiri

Molecular and microbial biochemistry to understand biological systems

The overarching themes of our research are to address the global issues of antimicrobial resistance and agricultural methane emissions. We aim to use the knowledge gained from our research to develop novel and improved strategies for human health and climate outcomes. Our current projects are focused on understanding how M. tuberculosis can become pathogenic after extended periods of an apparent dormant state and discovery of secondary metabolites for use as novel antibacterials.

Shaun Lott

Molecular and microbial biochemistry to understand biological systems

We are currently focussed on the enzyme RNase HI, which is responsible for digesting R-loops in cells. R-loops are DNA/RNA hybrid structures that are formed during mRNA production, which cause genomic damage if not removed. We have identified a set of compounds that inhibit RNase HI in Mycobacterium tuberculosis (the causative agent of TB) and synergise with existing antibiotics. We have also recently shown that RNase HI is a valid and druggable target in Neisseria gonorrhoeae. This project has been funded by the Maurice Wilkins Centre for Molecular Biodiscovery.

Iain Hay

Understanding the bacterial cell surface and cellular envelope – the interface through which bacteria interact with the world

We are a multi-disciplinary lab focused on studying the cellular biology of bacteria. We employ various microbiological, structural, biochemical, genetic, and imaging techniques to understand how bacterial cells work. We have expertise in the in vitro and in vivo characterisation of bacteria and bacterial protein complexes, using various methods, including classic molecular biology, cryo-electron microscopy, in vivo crosslinking, super-resolution microscopy, and genetic screens. We have a particular interest in understanding the bacterial cell surface and cellular envelope – the interface through which bacteria interact with the world. More than a third of bacterial proteins reside within this envelope or must traverse it via secretion. We aim to understand how bacteria produce and maintain this cell envelope, and how macromolecules (proteins, secretion systems, toxins, polysaccharides, phage…) are assembled into, and transported through this multifaceted environment. 

Stephanie Dawes

Using synergy to combat antibiotic resistance

Senior Research Fellows Stephanie Dawes and Andrew Thompson, and Associate Professor Shaun Lott from the University of Auckland are working with collaborators at the Universities of Waikato and Otago to determine whether inhibitors against a ubiquitous enzyme that degrades RNA:DNA hybrids in the cell can rescue antibiotics currently used to treat tuberculosis and gonorrhoeae. The enzyme is called Ribonuclease HI, or RNase HI for short. It carries out a very important role in the cell by degrading abnormal DNA:RNA hybrid molecules that can form in the genome after transcription, and which block polymerases from replicating the genome or transcribing genes. The hybrids also make the genome very sensitive to breakage, something that can be lethal for cells. If cells are unable to remove these hybrids, they become very sensitive to antibiotics that target transcription, translation and genome maintenance, which leads to the possibility even cells that are resistant to these antibiotics can be re-sensitized in combination with RNase HI inhibitors. These researchers are using genetic means to reduce RNase HI activity for proof of principle, and then looking for inhibitors of RNase HI to show that chemical inhibition can provide the same effect. The goal is to prolong the use of, or even rescue the antibiotics that we already have, and minimize the opportunity for resistance to arise. Ultimately they want to provide a general roadmap for new drug development, where synergy with other antibiotics or adjuvants is a key consideration in the initial selection of target.

Nobuto Takeuchi

The impact of horizontal gene transfer on bacterial genome evolution

Our research delves into the intricate roles of mobile genetic elements (MGEs), such as plasmids and phages, in shaping bacterial genome evolution, with a focus on antibiotic resistance and virulence factors. Using comparative genomics and simulation modelling, we investigate the distinct roles that different MGEs play in sculpting bacterial genomes. We also explore the coevolutionary dynamics between MGEs and bacterial genomes, as well as among different MGEs, to better understand the principles governing the evolution and organisation of bacterial gene pools.