Discovery Early Career Researcher Award - Grant ID: DE230100356
Funder
Australian Research Council
Funding Amount
$450,241.00
Summary
Bacterial membrane remodelling and the interaction with peptides. This project aims to elucidate the fundamental mechanism of lipid remodelling in Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplays between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and ....Bacterial membrane remodelling and the interaction with peptides. This project aims to elucidate the fundamental mechanism of lipid remodelling in Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplays between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and biophysical approaches. Novel knowledge will be generated to improve our understanding on how bacteria remodel their outer membrane in response to environmental stress. This will benefit the future design of much-needed antimicrobial strategies including products and technologies to target bacterial membrane. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100931
Funder
Australian Research Council
Funding Amount
$453,237.00
Summary
Molecular insights into the allosteric regulation of opioid receptors. Allosteric regulation is the biological process by which molecules bind to proteins someplace other than their active site, regulating their activity. Proteins on the cell surface called membrane receptors can be allosterically regulated to fine-tune the response of cells to the environment. This project aims to investigate how small molecules regulate receptor activity at a molecular level, using opioid receptors as an exemp ....Molecular insights into the allosteric regulation of opioid receptors. Allosteric regulation is the biological process by which molecules bind to proteins someplace other than their active site, regulating their activity. Proteins on the cell surface called membrane receptors can be allosterically regulated to fine-tune the response of cells to the environment. This project aims to investigate how small molecules regulate receptor activity at a molecular level, using opioid receptors as an exemplar system. I will use an interdisciplinary approach that combines structural biology, medicinal chemistry, analytical pharmacology, and cell biology. The knowledge gained from these studies will advance fundamental understanding of receptor function and can lay the foundation for future drug discovery efforts.Read moreRead less
The Role Of Nitric Oxide In The Regulation Of Skeletal Muscle Glucose Uptake During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participa ....When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participate in blood flow, nerve transmission and immune function, appears to be a necessary component for muscle glucose uptake at rest and during exercise. We have shown that blocking muscle NO production substantially reduces leg glucose uptake during exercise. The aim of this project is to verify this finding and to determine the mechanisms underlying this result. One way we intend to do this is to see whether a drug (Viagra) which increases the effects of NO, raises muscle glucose uptake at rest and during exercise. In rats, a drug almost identical to Viagra stimulates muscle glucose uptake. If Viagra is shown to increase glucose uptake this information may provide the initial human data necessary to develop new drugs to lower blood glucose levels in people with diabetes.Read moreRead less
The physiological importance of GLP-1R and GIPR dimerisation. Cell surface receptors are vital for relaying information from hormones to the cell to influence cell function, and ultimately physiological responses. Receptors can form oligomers with other receptors, but whether this can influence cellular and physiological responses is not yet defined. This biology-based project aims to bridge this knowledge gap by studying the dimerisation between two related receptors involved in whole body meta ....The physiological importance of GLP-1R and GIPR dimerisation. Cell surface receptors are vital for relaying information from hormones to the cell to influence cell function, and ultimately physiological responses. Receptors can form oligomers with other receptors, but whether this can influence cellular and physiological responses is not yet defined. This biology-based project aims to bridge this knowledge gap by studying the dimerisation between two related receptors involved in whole body metabolic homeostasis. Our team will deliver new knowledge into the disciplines of pharmacology, cellular biology, metabolism and physiology, and provide interdisciplinary research training to students and junior scientists, and strengthen research collaboration within and outside of Australia.Read moreRead less
Structure and dynamics of class B1 G protein coupled receptors . Cells within our body require cell surface proteins (receptors) to convert extracellular stimuli into an appropriate biological response. G protein-coupled receptors are the largest group of cell surface receptors. This project focuses on a subset of these receptors that have diverse and important functions in the central nervous system and the periphery, however there are many unanswered questions regarding the structure of these ....Structure and dynamics of class B1 G protein coupled receptors . Cells within our body require cell surface proteins (receptors) to convert extracellular stimuli into an appropriate biological response. G protein-coupled receptors are the largest group of cell surface receptors. This project focuses on a subset of these receptors that have diverse and important functions in the central nervous system and the periphery, however there are many unanswered questions regarding the structure of these proteins, and how they regulate cellular signalling. The primary outcomes of this project will provide detailed mechanistic insights on how receptors bind their stimuli and how this results in in their activation to mediate fundamental signalling that is important for all living organisms.Read moreRead less
Aerobic Exercise To Improve Cardiovascular And Neurological Health Outcomes In The Chronic Stroke Population
Funder
National Health and Medical Research Council
Funding Amount
$147,274.00
Summary
Physical activity is beneficial to people of all ages, to maintain heart health and brain function in relation to things like memory and complex thinking. Exercise is particularly important as we get older, especially after health problems such as heart attack or stroke, but it can be difficult to exercise safely at this time. This research project will develop an exercise program for individuals following stroke that is likely to improve fitness, heart and brain health and well-being.
Understanding and controlling neuropeptide GPCR-transducer coupling. G protein-coupled receptors (GPCRs) are physiologically essential, yet the spatiotemporal complexity of receptor function has limited our understanding of their function and success in drug development. Using a multi-disciplinary approach integrating GPCR signalling, trafficking and drug delivery, this research program aims to understand, and control, the molecular mechanisms that enable a single receptor to respond to differen ....Understanding and controlling neuropeptide GPCR-transducer coupling. G protein-coupled receptors (GPCRs) are physiologically essential, yet the spatiotemporal complexity of receptor function has limited our understanding of their function and success in drug development. Using a multi-disciplinary approach integrating GPCR signalling, trafficking and drug delivery, this research program aims to understand, and control, the molecular mechanisms that enable a single receptor to respond to different ligands to promote unique cellular processes. The anticipated outcomes include an enhanced capacity for understanding fundamental biology, and stronger national and international collaborations. It will provide significant benefits including expanded basic knowledge and advancement of drug delivery technology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101233
Funder
Australian Research Council
Funding Amount
$447,237.00
Summary
Developing the toolbox of compounds that target acid-sensing proteins. This project aims to examine the interaction between acid-sensing proteins and their modulatory compounds. Animals, including humans, must sense changes in environmental acidity to successfully interact with the surrounding world. Expected outcomes of the project include a better understanding of which regions of these proteins detect acidity, and to develop new compounds that modulate the proteins’ function. This would advan ....Developing the toolbox of compounds that target acid-sensing proteins. This project aims to examine the interaction between acid-sensing proteins and their modulatory compounds. Animals, including humans, must sense changes in environmental acidity to successfully interact with the surrounding world. Expected outcomes of the project include a better understanding of which regions of these proteins detect acidity, and to develop new compounds that modulate the proteins’ function. This would advance our fundamental knowledge in the physiological process of acid sensing. This expects to provide significant benefits, by aiding the potential development of agrochemicals and pain-relieving medications that regulate acid-sensing protein function, resulting in economic benefit to Australia via these new products.
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The Role Of Exercise Intervention In The Management And Prevention Of Insulin Resistance In Reproductive Aged Women
Funder
National Health and Medical Research Council
Funding Amount
$57,342.00
Summary
Research will focus on the use of exercise intervention in two insulin resistant groups of reproductive aged women including women at high risk of gestational diabetes and with polycystic ovary syndrome. Insulin resistance, if left unmanaged has long term health implications and information gained from the research would provide valuable information on the efficacy of exercise intervention and its role in treatment-prevention of complications of these common conditions.