Heras - Structural Biology and Bacterial Pathogenesis laboratory
Our laboratory conducts strategic, multidisciplinary research to understand how harmful bacteria cause disease and evade antibiotics. Antimicrobial resistance (AMR) is a growing global health crisis, responsible for thousands of deaths and threatening the effectiveness of current medical treatments. In response to this urgent challenge, we integrate structural biology, biochemistry, and microbiology to study key bacterial proteins involved in pathogenesis and resistance. By determining their atomic structures and revealing how they function, we uncover how bacteria build the molecular machinery needed to infect hosts and survive antibiotic treatment.
Using these insights, we are developing innovative therapeutics that target bacterial virulence rather than viability — a strategy designed to reduce the selective pressure that drives resistance. Our work includes the discovery of small-molecule and antibody-based inhibitors that block critical bacterial processes such as protein folding and biofilm formation. These efforts support the global search for next-generation antimicrobials and address the pressing need for new treatments against high-priority, drug-resistant pathogens identified by the World Health Organization.
Research areas
Structural Biology of Bacterial Virulence Factors
We investigate how bacterial pathogens assemble and deploy proteins that enable infection. A major focus is on autotransporters and other outermembrane proteins that promote adhesion, toxicity, and biofilm formation. These proteins play essential roles in establishing infection and are also promising therapeutic targets. By solving the atomic structures of these virulence factors, we gain deep insight into their mechanisms of action. This work has been supported ARC and NHMRC, which has provided the foundation for the development of new therapeutics that to block infections.
Many bacterial virulence factors and resistance enzymes require precise folding to function, often mediated by redox-active proteins such as the Dsb family. Our lab is a global leader in the structural and functional characterisation of these folding catalysts. This work has been consistentlysupported by ARC, NHMRC and philanthropy. Read more in Nature Reviews Microbiology [external link]
We are now expanding this work to study MarR-family redox-responsive transcriptional regulators, with support from ARC Discovery Project DP250102263. By investigating how these proteins sense stress and regulate gene expression, we aim to uncover novel points of intervention in bacterial pathogenesis and antibiotic resistance.
Disarming Pathogens: Targeting Virulence and Biofilms to Combat Antimicrobial Resistance
Antibiotic resistance is driven by treatments that kill or inhibit bacterial growth, selecting for resistant strains. Our lab is developing new strategies that target bacterial virulence and biofilm formation—key contributors to infection severity—without affecting bacterial viability. By disarming pathogens rather than killing them, we aim to reduce the selective pressure that leads to resistance. We focus on mechanisms such as protein folding and the formation of biofilms—protective bacterial communities that make infections more persistent and harder to treat.
Through support from programs including Australia’s Economic Accelerator (AEA–Ignite), we are translating this research into next-generation therapeutics. Our team is developing small-molecule inhibitors and monoclonal antibodies that block the assembly of virulence determinants. For example, we have developed and patented biologics with antibiofilm activity, which represent a novel approach endorsed by WHO innovation criteria and hold promise for treating chronic and drug-resistant infections.
