Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological pr ....Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological processes including cell-to-cell communication. The outcomes of this study will include new knowledge of this process and chemical modifiers of this transport protein. This project will benefit structural biology and biophysics training and may lead to the development of novel compounds that can be used to explore function. 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
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
How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowled ....How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100144
Funder
Australian Research Council
Funding Amount
$1,225,000.00
Summary
High Performance Single Crystal X-ray Diffraction Facility. This project aims to establish an advanced multidisciplinary facility for the structural characterisation of chemical and biological molecules. Through providing a broad suite of advanced capabilities, including measurement under a range of conditions and rapid crystal screening, the project expects to greatly accelerate research efforts across a wide spectrum of the molecular sciences. Expected outcomes include detailed understandings ....High Performance Single Crystal X-ray Diffraction Facility. This project aims to establish an advanced multidisciplinary facility for the structural characterisation of chemical and biological molecules. Through providing a broad suite of advanced capabilities, including measurement under a range of conditions and rapid crystal screening, the project expects to greatly accelerate research efforts across a wide spectrum of the molecular sciences. Expected outcomes include detailed understandings of the structures and functions of an array of scientifically and technologically important systems, spanning materials, proteins and pharmaceuticals. This should provide significant benefits, both in advancing the understanding of these systems and in spurring commercial development and application.Read moreRead less
Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown t ....Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown to respond to mechanical stimuli in the same manner as mechanoreceptor channels of organisms from bacteria to humans the intended outcome of this project is to uncover the unifying principles of mechanotransduction anchored in the laws of physics and chemistry that have guided the force-dependent design of all life forms.Read moreRead less
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
Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected ....Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected to help guide the development of new agents for selectively delivering imaging and biologically active agents to cells.Read moreRead less