Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
Computational enzymology: exploring the free energy landscape of enzymatic catalysis. Most biochemical reactions depend on enzyme catalysis and understanding how enzymes work at the molecular level remains a central question. This project will develop a suite of computational models to study the mechanisms of enzyme-catalysed reactions and such knowledge holds promise for technological benefits in the form of new drugs and novel catalysts.
Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project ....Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project outcomes are intended to lead to significant advances in membrane protein structure determination and will have a substantial impact on future research in the pharmaceutical industry.Read moreRead less
Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting p ....Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting proteins of marine algae. Understanding the link between structure and quantum effects could improve our knowledge of how nature achieves its remarkable efficiency in utilising the energy from the sun. This is likely to foster new technologies that improve the efficiency of solar energy systems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100090
Funder
Australian Research Council
Funding Amount
$640,000.00
Summary
A centre for structural cryo-electron microscopy. This equipment will use powerful microscopes to visualise the shape of proteins. The data generated in the facility will provide fundamental insight into how large complex proteins govern life-and-death events in biology. These data will be important for scientists to develop new approaches to control aberrant protein function in disease.
New methods for structure analysis of proteins and protein interactions. This project will advance nuclear magnetic resonance (NMR) technologies pioneered at the Australian National University which employ site-specific attachment of paramagnetic metal tags to proteins. A new and diverse set of strategies will dramatically extend the range of applications to targets of interest in the fight against cancer and bacterial infections.
The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to ....The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to understand how MPEG1 interacts with the interferon signalling pathway. These data will provide fundamental insight into how perforin-like proteins are controlled and will broadly inform new approaches to modify immune function and molecular signalling events.Read moreRead less
Structural analysis of poxviruses: advancing our understanding of complex DNA viruses and their in vivo crystals. This project will use innovative structural biology approaches to investigate two key particles of poxviruses, the largest viruses infecting humans. Advance in understanding of immature particles and natural crystals of poxviruses will provide the basis for the development of broad-spectrum antivirals and novel microparticles for vaccine-delivery.