Discovery Early Career Researcher Award - Grant ID: DE190101244
Funder
Australian Research Council
Funding Amount
$342,411.00
Summary
Unravelling the relationship between food and the brain. This project aims to investigate how highly palatable foods that are high in fat and sugar, interact with the brain to cause their overconsumption. Highly palatable foods cause plasticity in brain reward circuitry in a manner similar to drugs of abuse. Identifying how these "junk" foods interact with reward areas of the brain will explore the neural mechanisms underlying the hedonic nature of appetite. This project will not only inform our ....Unravelling the relationship between food and the brain. This project aims to investigate how highly palatable foods that are high in fat and sugar, interact with the brain to cause their overconsumption. Highly palatable foods cause plasticity in brain reward circuitry in a manner similar to drugs of abuse. Identifying how these "junk" foods interact with reward areas of the brain will explore the neural mechanisms underlying the hedonic nature of appetite. This project will not only inform our understanding of how exposure to these foods can contribute to overeating and obesity, a huge and growing problem in Australia, but will also provide evidence to inform policy options relevant to advertising and marketing of these foods.Read moreRead less
Novel mechanisms for regulating the retinal vasculature. Tight control of the retinal vasculature is crucial for maintaining normal vision. Unlike most blood vessels in the body, those in the retina and brain receive no direct neural control. Rather they rely on support cells to communicate the needs of neurons. This project aims to examine the mechanisms by which resident immune cells, called microglia, regulate retinal capillaries in response to neural activity. New knowledge examining a novel ....Novel mechanisms for regulating the retinal vasculature. Tight control of the retinal vasculature is crucial for maintaining normal vision. Unlike most blood vessels in the body, those in the retina and brain receive no direct neural control. Rather they rely on support cells to communicate the needs of neurons. This project aims to examine the mechanisms by which resident immune cells, called microglia, regulate retinal capillaries in response to neural activity. New knowledge examining a novel mechanism will be generated. This information is crucial for enhancing our understanding of how blood vessels are controlled in the retina and brain and will guide the development of novel ways of examining blood vessel function.Read moreRead less
Microfluidic models of the CNS: Understanding cells, circuits & synapses. Aims: We aim to develop new cell culture platforms to form defined networks of brain cells. These platforms will be used to determine the critical mechanisms underpinning central nervous system function.
Significance: The devices developed will enable an unprecedented capacity to monitor changes throughout a network, with analysis at the level of the synapse, cell and circuit.
Expected outcomes: We will advance knowledge ....Microfluidic models of the CNS: Understanding cells, circuits & synapses. Aims: We aim to develop new cell culture platforms to form defined networks of brain cells. These platforms will be used to determine the critical mechanisms underpinning central nervous system function.
Significance: The devices developed will enable an unprecedented capacity to monitor changes throughout a network, with analysis at the level of the synapse, cell and circuit.
Expected outcomes: We will advance knowledge regarding the function of the CNS and deliver complex human cellular systems, that have both discovery and commercial applications.
Benefit: These platforms will have subsequent application revealing the mechanisms underlying numerous neurological diseases, with capacity to upscale for rapid drug screening.
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Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project out ....Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist the production of meat by managing hypothermia and hyperthermia risk in agriculture.Read moreRead less
A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To un ....A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To understand how the method can be optimized, the thermodynamic pathway of membrane disruption will be investigated at a single cell level. The methods and insights arising from this project could eventually lead to novel, patentable and lower-cost health technologies.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by ....Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by implementing innovative approaches.
Expected Outcomes: Expected outcomes include significant new knowledge and a new multi-disciplinary platform for measuring peptide absorption.
Benefits: This should provide significant benefits by informing the future design of peptides for supplements, therapeutics and carriers. Read moreRead less
Understanding the determinants of age-related muscle wasting in females . This project aims to investigate the fundamental mechanisms underlying age-related muscle wasting in females. Females live longer than males and are more susceptible to the consequences of muscle ageing. Yet, our current knowledge is overwhelmingly inferred from findings from male cohorts. By comprehensively mapping the functional, molecular and epigenetic mechanisms of ageing in female muscle, this project will generate n ....Understanding the determinants of age-related muscle wasting in females . This project aims to investigate the fundamental mechanisms underlying age-related muscle wasting in females. Females live longer than males and are more susceptible to the consequences of muscle ageing. Yet, our current knowledge is overwhelmingly inferred from findings from male cohorts. By comprehensively mapping the functional, molecular and epigenetic mechanisms of ageing in female muscle, this project will generate new, fundamental knowledge that will allow a unique interpretation of previous research through a sex-specific lens. This knowledge will contribute to better inform sex-specific models of research and practice in the future, ultimately delivering economic and social benefits for Australia and international communities.Read moreRead less
Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the ....Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the metabolic pathways responsible for nutrient sensing and regulation of protein synthesis remain unresolved. The project will assess defective amino acid sensing and protein synthesis in old mammals, identifying the role of glycine signalling in these processes. The project expects to underpin development of muscle-specific modulators of muscle homeostasis with broad relevance to Australia’s ageing population.Read moreRead less