How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following ner ....Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following nervous system injury and the importance of microtubule modifying proteins in promoting regeneration. This should provide significant benefits in our understanding of the cellular mechanisms behind nervous system repair, and offer new approaches for promoting regeneration after injury.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101511
Funder
Australian Research Council
Funding Amount
$424,816.00
Summary
Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) unde ....Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) understanding the structural mechanisms underlying GPCR activation, (ii) biased agonism and (iii) G protein selectivity. This should provide significant benefits, such as advancement of fundamental knowledge in GPCR biology and pharmacology that could also one day lead to therapeutic development.Read moreRead less
Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model t ....Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model to generate new knowledge of the cellular and genetic components that drive evolution of different brain parts and shapes the vertebrate brain. In doing so the project aims to provide research training, excellence and knowledge that in future may benefit health and the society. Read moreRead less
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.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
Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected out ....Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected outcomes:
We will identify a new mechanism that governs tissue development, and introduce new imaging and genetic technologies to the Australian research community.
Benefit:
We expect potential economic and commercial interest in development of new gene analysis tools and biotechnological tissue manipulation applications.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
Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This k ....Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This knowledge will reveal how IPO5 controls formation of sperm by revealing what other proteins it binds to and how this affects cell signaling and responses to the environment.
Benefits: This will provide information about potential interventions to control fertility or to repair abnormal cells.
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Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractab ....Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of cell and developmental biology.Read moreRead less