Antibiotics have catalysed the greatest revolution in modern medicine, saving millions of lives annually. 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 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 resistanceThe Dowton group is directed at understanding how DNA molecules evolve with particular interest in the mitoochondrial genome, which has remarkably little non-coding DNA. For example, protein-coding regions account for 70% of the mitochondrial genome in humans, but only 1% of the nuclear genome. Genes are sandwiched together, often with only a few non-coding nucleotides between them. This has resulted in remarkable stability in the arrangement of genes, as any gene movement is likely to disrupt the function of a neighbouring gene; many genes are in precisely the same position that they were in hundreds of millions of years ago. Our research has focussed on one lineage of animals that have broken this trend. The Hymenoptera (ants, bees and wasps) have mitochondrial genomes whose genes change positions relatively frequently. By sequencing related hymenopteran mitochondrial genomes, we can identify the sorts of changes that have occurred, and better understand the fundamental mechanism of mitochondrial gene rearrangement.
View Professor Mark Dowton's Scholars page
Contact mark_dowton@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.
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 haibo_yu@uow.edu.au for more information.