Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less
Role of suppressor of cytokine signalling proteins (SOCS3) in defective muscle repair and ageing. Old muscles are slower and weaker than young muscles, they are injured more easily and they repair less successfully. This proposal investigates the role of SOCS3-signalling in muscle repair, ultimately to improve healing and to promote healthy ageing that will enable older Australians to enjoy a better quality of life.
The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle ma ....The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle mass ensures international competitiveness, productivity and economic growth, and successful ageing, where maintaining muscle mass is essential.Read moreRead less
Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 defici ....Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 deficient animals are 40 percent larger than normal. Consequently, we wish to determine how SOCS-2 acts to limit the size of an animal and whether this involves regulation of growth hormone action.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100859
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Phosphatidylserine: a regulator of muscle and mitochondrial biology? This project aims to characterise a novel pathway involved in regulating skeletal muscle mass through effects on mitochondrial function. This project will examine how degradation causes mitochondrial abnormalities leading to severe muscle wasting. This project is expected to advance understanding of how pathways interact, thus identifying novel mechanisms that impact on muscle structure and function. Understanding what makes mu ....Phosphatidylserine: a regulator of muscle and mitochondrial biology? This project aims to characterise a novel pathway involved in regulating skeletal muscle mass through effects on mitochondrial function. This project will examine how degradation causes mitochondrial abnormalities leading to severe muscle wasting. This project is expected to advance understanding of how pathways interact, thus identifying novel mechanisms that impact on muscle structure and function. Understanding what makes muscle vulnerable to atrophy is fundamental to developing strategies to counteract muscle wasting conditions. Methodologies developed will have broad application in the field of life sciences research.Read moreRead less
From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a nov ....From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a novel and unique way. This combination is in itself a major advancement of scientific methods that will accelerate discovery in the field of systems biology. In this respect, the project is a premier example of the priority goal Breakthrough Science and of the national research priority Frontier Technologies.Read moreRead less
Mapping and defining inter-organ cross talk during exercise. This project aims to examine precisely how organs communicate and interact. These interactions are particularly important during exercise, when continued movement demands intricate organ communication, and have major ramifications for the whole organism as it ages. Precisely how this communication takes place is unclear, but we now know that the movement of cargo with extracellular vesicles (EVs) plays an integral role in organ to orga ....Mapping and defining inter-organ cross talk during exercise. This project aims to examine precisely how organs communicate and interact. These interactions are particularly important during exercise, when continued movement demands intricate organ communication, and have major ramifications for the whole organism as it ages. Precisely how this communication takes place is unclear, but we now know that the movement of cargo with extracellular vesicles (EVs) plays an integral role in organ to organ communication. This project expects to build upon unprecedented recent developments we have made in the biology of inter-organ communication via EVs. The expected outcomes will have broad impact across life science and biotechnology.Read moreRead less
Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to u ....Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to utilise this technology to identify novel insulin-sensitising agents. These agents will be used for drug discovery purposes by our industry partner ChemGenex and as novel tools to dissect the mechanism of insulin action.Read moreRead less
ION CHANNELS FORMED BY SMALL PROTEINS FROM VIRUSES. Movements of ions across cell membranes through protein ion channels are essential for normal cell function. We have found that some small proteins from viruses can form ion channels. Studying these simple channels should give us clues about the function of more complex channels, such as those in the brain, as well as giving us information about the viruses themselves. We will test whether a small protein from Ross River virus forms ion channel ....ION CHANNELS FORMED BY SMALL PROTEINS FROM VIRUSES. Movements of ions across cell membranes through protein ion channels are essential for normal cell function. We have found that some small proteins from viruses can form ion channels. Studying these simple channels should give us clues about the function of more complex channels, such as those in the brain, as well as giving us information about the viruses themselves. We will test whether a small protein from Ross River virus forms ion channels and will also test the effects of selected mutations in proteins from influenza and AIDS viruses that we have shown previously to form ion channels.Read moreRead less