Undermining fungal defences by targeting their functional amyloid armour. This project will determine how a protective protein coating forms on the surface of fungal spores and infectious structures. This coating is comprised of amyloid protein fibrils and is used by fungi to improve efficiency of infection and to avoid detection by the host plant or animal. We have discovered novel small molecules that prevent the fibrils from forming. This project will use these molecules to reveal the details ....Undermining fungal defences by targeting their functional amyloid armour. This project will determine how a protective protein coating forms on the surface of fungal spores and infectious structures. This coating is comprised of amyloid protein fibrils and is used by fungi to improve efficiency of infection and to avoid detection by the host plant or animal. We have discovered novel small molecules that prevent the fibrils from forming. This project will use these molecules to reveal the details of the fibril assembly mechanism and find the best way to undermine this fungal defence system. This knowledge will enable the development of potent small molecule inhibitors to treat fungal infections that blight crops and harm animals, and the production of new layered biomaterials for nanotechnology applications.Read moreRead less
Understanding chaperone function, one molecule at a time. This project aims to determine how molecular chaperones, a class of proteins represented in all phyla of life, work together to keep proteins folded and functional, particularly following cellular stress. This is important as proteins are involved in virtually all biological processes. This project will exploit innovative microscopy techniques to watch these molecular chaperones as they work. Expected outcomes of this project are the firs ....Understanding chaperone function, one molecule at a time. This project aims to determine how molecular chaperones, a class of proteins represented in all phyla of life, work together to keep proteins folded and functional, particularly following cellular stress. This is important as proteins are involved in virtually all biological processes. This project will exploit innovative microscopy techniques to watch these molecular chaperones as they work. Expected outcomes of this project are the first definitive description of how molecular chaperones interact to refold proteins, and the development of novel methods to study dynamic biological processes. This should provide significant benefits including enhanced collaboration and scientific capacity in Australia.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101536
Funder
Australian Research Council
Funding Amount
$473,824.00
Summary
How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the mole ....How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the molecular mechanisms that allow heme to enter cells and regulate blood vessel growth in the brain. The outcomes of this research will enhance our understanding of the brain’s core infrastructure and will contribute to an understanding of how cerebral blood vessels grow and maintain integrity. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100780
Funder
Australian Research Council
Funding Amount
$455,237.00
Summary
Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecul ....Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecular visualisation technologies, leading to the first molecular description of dynamic processes used by the human replisome. Benefits include improved understanding of a fundamental biological process that often malfunctions in cancers, development of novel methodology, and interdisciplinary training.Read moreRead less
High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. Wit ....High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. With this new technology we aim to identify DNA polymerases with improved performance that benefit biotechnological applications. Additionally, these single-molecule directed-evolution methods will benefit the wider scientific community and lay the foundation for further advances in directed evolution.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101236
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of ho ....Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of how specific modifications modulate protein and cellular function. Significant benefits of this interdisciplinary project include access to a new class of molecules for basic research that may also find use for cell engineering applications within the growing biotechnology sector in Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100029
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the bo ....High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the body, investigating mechanisms of brain plasticity in predictive learning, understanding the molecular pathways involved in neurodegeneration and cancer, developing novel methods for multi-modal image analysis, and developing and validating new radiation detectors for the next generation of imaging technology.Read moreRead less