Discovery Early Career Researcher Award - Grant ID: DE240101055
Funder
Australian Research Council
Funding Amount
$448,737.00
Summary
How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The bene ....How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The benefits of these outcomes include generation of knowledge on the impact of tissue stiffness on the signalling mechanisms that drive formation and maintenance of blood vessels. In the long term, this fundamental understanding could give rise to major developments in emerging industries such as organ bioengineering.Read moreRead less
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100149
Funder
Australian Research Council
Funding Amount
$590,000.00
Summary
Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit D ....Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit Direct Electron Detection camera system into the established cryo-EM facility managed by the University of Queensland node of the Australian Microscopy and Microanalysis Facility. This will offer unique and significantly improved capabilities for atomic resolution protein structure analysis, and will support a broad range of projects across the biological sciences.Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100164
Funder
Australian Research Council
Funding Amount
$310,000.00
Summary
A facility for ex-vivo molecular imaging. The facility will allow a consortium of Australian researchers to create an integrated facility for imaging biological receptors in tissue, bringing together laboratory, radiochemistry and imaging expertise. Digital data at each site will be able to be viewed and analysed remotely.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100066
Funder
Australian Research Council
Funding Amount
$443,311.00
Summary
Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided ....Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided by the high-throughput, automated patch clamp system is that it allows up to 384 cells to be recorded simultaneously. This project expects to enhance capacity to automate and standardise the quality of recordings, substantially increase the rate of data production, and enable greater access to patch clamp technology.Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less