Antimicrobial Resistance

Antimicrobial Resistance

Antibiotics have allowed what some might call the greatest revolution in modern medicine, saving millions of lives every year. However, the rapid rise in resistance of bacterial infections against these miracle drugs presents a major health threat. By integrating academic disciplines and working with stakeholders in the health, pharma, biotech, and agriculture sector we aim to develop new and effective solutions.

Superbugs: how UOW researchers are curbing antimicrobial resistance

Superbugs are considered a 21st-century health challenge, so how can we combat antimicrobial resistance and what impact will it have on health outcomes?

Learn more about UOW research into antimicrobial resistance

In the race to stay one step ahead of infectious disease we seem to be losing.
 
All the health challenges in a more multinational way
 
Drug-resistant diseases flavonoids of around 700,000 people each year
 
 
Looking at the Molecular Mechanisms that cause an activity
 
It has an imediate effect.
 
The main culprit is an over prescription of Antibiotics

Research groups

Life is driven by chemistry. Digesting food, contracting muscle, eyesight, and all of the other processes that keep us alive are driven by it. Physicist Richard Feynman said “it is very easy to answer many of these fundamental biological questions; you just look at the thing!” Knowing the three-dimensional shapes of important biological molecules can help us understand how they work. Knowing their structure can inform the discovery of therapeutic agents. So how do we “see” the structures of biological molecules? We use a technique called X-ray diffraction and computational techniques to study the structure and dynamics of two important classes biological molecules: proteins and nucleic acids.

Our research is exemplified by the following projects:

  • Bacterial DNA clamps are proteins that slide along DNA. They are required for bacterial survival and represent an excellent target for antibiotic development. With Prof Nick Dixon and A/Prof Michael Kelso (SCMB), and Dr Andy McElroy (The Research Network, UK) we are developing compounds that block important interactions involving bacterial DNA clamps.
  • Human glutathione transferase Omega 1 (GSTO1-1) plays an essential role in bacterial lipopolysaccharide (LPS) stimulated inflammatory responses through Toll-like receptor 4 (TLR4). This protein is a target for the development of inhibitors that could limit the massive innate immune response that produces damaging inflammatory cytokines and reactive oxygen species. We are working with the John Curtin School of Medical Research and the Monash Institute of Pharmaceutical Sciences to develop inhibitors.

View Associate Professor Aaron Oakley's Scholars page

Contact aarono@uow.edu.au for more information.

The Pyne group’s interests are concerned with the application of organic chemical synthesis to the preparation of novel and biologically relevant heterocyclic compounds for new drug discovery. Our current collaborative projects include:

  1. Azasugar alkaloids and their analogues as alpha-glycosidase inhibitors with potential applications as anti-diabetic and anti-obesity drugs.
  2. New N- and O-heterocycles via novel metal-catalyzed reaction discovery (with C. Hyland)
  3. Cationic peptides for the discovery of new antibacterial agents to fight pathogenic bacteria including Clostridium difficile involved in gut infections (with P. Keller and H.Yu).

We are also collaborating with scientists in SE Asia (Thailand, Vietnam and Indonesia) and Nigeria on studying traditional medical plants for the discovery of new antibacterial, anti-cancer and anti-malarial agents.

View Professor Stephen Pyne's Scholars page

Contact spyne@uow.edu.au for more information

The Tolun group studies the bio-nano-machines carrying out processes involving nucleic acids such as DNA recombination, replication, repair and RNA transcription. We use molecular imaging (electron microscopy), structural biology (Cryo-EM), biochemistry and molecular biology.

Tolun Group members standing out the front of the Molecular Horizons Building

The main technique utilised in my group is electron microscopy (EM). In addition to the state-of-the-art cryo-EM, we also use the classical EM techniques such as shadow-casting (i.e., metal shadowing) and negative staining. Shadow-casting is a technique ideally suited for visualising DNA and DNA-protein complexes at the single-molecule level.

DNA Recombination

Single strand annealing homologous DNA recombination (SSA) is a process found in virtually all life. It is particularly important in the double-strand DNA (dsDNA) viruses, such as the oncogenic viruses Epstein-Barr Virus (EBV) Kaposi's sarcoma-associated herpesvirus (KSHV), and Herpes Simplex Virus 1 (HSV-1). SSA is catalysed by a protein complex called a two-component recombinase (TCR), composed of an exonuclease and an annealase. The exonuclease generates a single-strand DNA (ssDNA) overhang, and the annealase binds to this nascent ssDNA and anneals it to a homologous ssDNA strand.

My research group is using a multi-disciplinary approach to better understand how this machinery works, with a focus on cryo-EM. We are interested in determining the structures of proteins and protein complexes involved in SSA, using cryo-EM.

DNA Replication

In collaboration with the research groups of Nick Dixon, Antoine van Oijen, and Aaron Oakley, we are studying DNA replication to better understand the molecular mechanistic details of this process.

Collaborations

We are a very collaborative group, and in addition to our main interests above, we also work on many collaboration projects to determine the cryo-EM structures of proteins or complexes from other systems. Some of the topics we are working on with our collaborators include transcription, snake venom toxins and chaperons.    

View Dr Gökhan Tolun's Scholars page

Contact gokhan_tolun@uow.edu.au for more information

Our research efforts focus on developing and applying theoretical and computational tools to understand the structure-dynamics-function relationship in the complex (bio)molecular and nanoscale systems. Complementary to experimental investigations, such studies can gain new insights at the atomic level into the underlying mechanism and provide necessary knowledge for molecular engineering and discovery of novel therapeutics. Current research projects include computational studies of protein-ligand interactions, mechanistic studies of enzymatic reactions, and computer-aided enzyme design. 

View Associate Professor Haibo Yu’s Scholar page

Please contact hyu@uow.edu.au for more information.