Our researchers seek to understand the structure, functionality, and behaviour of biologically important molecules from the atomic to the macro-molecular scale. By combining cutting-edge techniques such as electron microscopy, mass spectrometry, and single-molecule imaging with computational and biochemical approaches, we aim to unravel the structure and behaviours of proteins to better understand their function.
The development and application of high-resolution mass spectrometry imaging methods to study localized chemical processes occurring within complex surfaces such as biological tissue and cells. MSI developments focus on are (i) improving spatial resolution; (ii) the types of molecules that can be detected using MALDI-based approaches; and (iii) techniques to unambiguously identify the detected molecules. Key application areas include visualizing and understanding alterations in lipid biochemistry occurring throughout heterogeneous tissues, and more generally, disease-induced bimolecular alterations that occurring within diseased tissues.
Contact sellis@uow.edu.au for information.
The Lewis Lab studies how DNA is copied inside our cells. This process, known as DNA replication, is fundamental to life. We focus on understanding how large molecular machines carry out replication, with particular interest in how this occurs in mitochondria, where many of the underlying mechanisms remain unclear. These systems are directly linked to cancer, mitochondrial diseases, and genome instability. To investigate these questions, we combine single-molecule imaging, cryo-electron microscopy, and biochemical reconstitution to observe replication in real time, capture structural detail at near-atomic resolution, and uncover molecular mechanisms that remain hidden in traditional experiments. Our goal is to understand how the components of the replication machinery work together, and how their breakdown can lead to disease. Alongside this, we develop new tools to better visualise and study complex biological systems. These technologies help us push the limits of what can be seen and measured, enabling new insights into how molecular machines function in health and disease.
The Single-Molecule Biophysics Lab develops advanced methods to visualise individual biomolecules in real time. We focus on pushing the limits of single-molecule imaging and analysis to uncover dynamic molecular behaviours hidden in ensemble experiments. Our technologies are used to reveal the fundamental mechanisms of DNA replication and genome maintenance. In parallel, we are applying these methods to directed evolution, using single-molecule readouts to evolve proteins and establish new biosensing strategies. Our goal is to create low-cost diagnostics platforms with single-molecule sensitivity. By combining technical innovation with biological discovery, we aim to expand the frontiers of both fundamental and applied molecular science.
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
The Wilson research group is focussed on both basic and applied science relating to chaperones and protein folding, with a special emphasis on a novel group of (normally secreted) extracellular chaperones discovered by us. We reported the first known extracellular chaperone in mammals (clusterin) and have continued to discover new examples of this small but growing family of important molecules. Our studies include in vitro structure-function studies of extracellular chaperones, and also encompass work in small animal models (Drosophila, zebrafish and C. elegans) addressing basic science questions and specific disease scenarios. We have also developed new fluorescence-based technology platforms, including a high-throughput flow cytometry system currently being applied in a search for novel drugs to treat motor neurone disease.
A 3-colour image of a stressed cell: nucleus (blue), endoplasmic reticulum (red) and a chaperone (BiP; green)
View Senior Professor Mark Wilson's Scholars page
Contact mrw@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.