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
Biomolecular condensates in mRNA-regulation in germ cells. This project aims to investigate how cells form microenvironments that are enriched for specific biological functions. Using a powerful combination of cutting-edge in vitro and in vivo experiments, the project will generate new knowledge in the emerging area of liquid-liquid phase separation. We will analyse the formation of germ granules that are required for fertility. The expected outcome is a transformational understanding of how liq ....Biomolecular condensates in mRNA-regulation in germ cells. This project aims to investigate how cells form microenvironments that are enriched for specific biological functions. Using a powerful combination of cutting-edge in vitro and in vivo experiments, the project will generate new knowledge in the emerging area of liquid-liquid phase separation. We will analyse the formation of germ granules that are required for fertility. The expected outcome is a transformational understanding of how liquid-liquid phase separation occurs in cells which, in the longer term, will have applications in biotechnology and disease treatment.Read moreRead less
Developing serial crystallography for room temperature structure & dynamics. This project aims to uncover the molecular structural dynamics of a bacterial enzyme responsible for protein folding in bacteria. This project expects to generate new knowledge to guide the development of a new type of antibacterial to circumvent antibiotic resistance. Expected outcomes of this project include new experimental, computational and simulation tools for dynamic X-ray crystallography including new capabiliti ....Developing serial crystallography for room temperature structure & dynamics. This project aims to uncover the molecular structural dynamics of a bacterial enzyme responsible for protein folding in bacteria. This project expects to generate new knowledge to guide the development of a new type of antibacterial to circumvent antibiotic resistance. Expected outcomes of this project include new experimental, computational and simulation tools for dynamic X-ray crystallography including new capabilities at the Australian Synchrotron for very small microcrystals of any biomolecule. This would provide a powerful new tool for the Australian structural biology community that should accelerate fundamental discoveries, including facilitating high-resolution structure determination of membrane proteins and drug development.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
Chemical-biology approaches to pathway selective adenosine receptor ligands. This project aims to develop new chemical-biology tools and approaches for selectively targeting signalling pathways mediated by G protein-coupled receptors (GPCR). GPCRs are an important family of cell surface signalling proteins that are responsible for the regulation of numerous vital physiological functions. The A1 adenosine receptor is an important model and therapeutically relevant GPCR that will be the focus of t ....Chemical-biology approaches to pathway selective adenosine receptor ligands. This project aims to develop new chemical-biology tools and approaches for selectively targeting signalling pathways mediated by G protein-coupled receptors (GPCR). GPCRs are an important family of cell surface signalling proteins that are responsible for the regulation of numerous vital physiological functions. The A1 adenosine receptor is an important model and therapeutically relevant GPCR that will be the focus of this project. Compounds known as bitopic ligands, which can interact with distinct binding sites (termed orthosteric and allosteric sites), will be explored as pathway selective agents capable of activating the signalling pathways mediating the desired effect in preference to those producing adverse effects. Longer-term benefits include the identification of bioactive compounds with more selective modes of action and improved safety profiles.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