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
Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC200100052
Funder
Australian Research Council
Funding Amount
$4,789,838.00
Summary
ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide signifi ....ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide significant benefits including advancing Australian biotechnological capacity and improved linkages with major pharmaceutical partners. It should also provide a substantive competitive advantage to nascent Australian biotechnology companies that also links into new National investment into drug discovery and development infrastructure.Read moreRead less
Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiolo ....Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiological stimuli to control electrical signalling the body. Our results will provide benefits in the form of basic understanding relevant to ion transport phenomena in biological systems, and atomic-level views of nervous system function to guide future directions in pharmacology.Read moreRead less
Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms t ....Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms that regulate the signalosomes. The intended outcome is to answer the long-standing question of control of speed and amplitude of innate immune response at the molecular level. Both locally and internationally, this new approach should provide benefits across structural biology, molecular evolution and biotechnology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100054
Funder
Australian Research Council
Funding Amount
$1,341,398.00
Summary
Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant ad ....Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant advantage for chemists, physicists, biologists, geologists, and engineers who rely on detailed structural knowledge to rationally optimise the properties of their compounds, from pharmaceutical activity to carbon capture to superconductivity, to the substantial benefit of multiple national priority areas.Read moreRead less
Elucidating the molecular basis of plant potyvirus resistance . Plant viruses are responsible for a large proportion of crop losses, and genetic resistance is currently the most effective means to control viral spread. This project investigates, on a molecular and structural level, host factors that plant viruses hijack during infection, and in particular, the mutations in these factors that confer resistance. We further aim to elucidate the mechanisms by which plant viruses overcome resistance ....Elucidating the molecular basis of plant potyvirus resistance . Plant viruses are responsible for a large proportion of crop losses, and genetic resistance is currently the most effective means to control viral spread. This project investigates, on a molecular and structural level, host factors that plant viruses hijack during infection, and in particular, the mutations in these factors that confer resistance. We further aim to elucidate the mechanisms by which plant viruses overcome resistance mediated by these host factors. A detailed understanding of the molecular interactions between plant viruses and their host will enable new, robust and more effective forms of resistance to be engineered. This work therefore has economic and environmental implications for agricultural productivity in Australia. Read moreRead less
Protecting cereal grain development at high temperatures. This project aims to investigate new temperature-responsive factors that regulate cereal grain development to protect grain production under heat stress. The new research will leverage international collaborations with access to cutting-edge genetic and technological resources, and refine novel X-ray imaging techniques in Australia, to observe how temperature affects flower structure and function in barley and rice. Favourable mutations t ....Protecting cereal grain development at high temperatures. This project aims to investigate new temperature-responsive factors that regulate cereal grain development to protect grain production under heat stress. The new research will leverage international collaborations with access to cutting-edge genetic and technological resources, and refine novel X-ray imaging techniques in Australia, to observe how temperature affects flower structure and function in barley and rice. Favourable mutations that optimise plant yield and fitness will be defined and explored in other, more complex, cereals such as wheat. Expected outcomes will be fundamental breakthroughs in understanding how plants respond to, and buffer, the effects of heat to lead to translational breeding strategies that bolster grain yield.Read moreRead less