The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less
Understanding the vesicle release mechanisms that regulate peripheral serotonin levels. The purpose of this project is to understand how serotonin is released into the circulation from specialised cells within the gut. As circulating serotonin controls multiple biological systems within the gut and throughout the body, the outcomes of this project will further understandings of the systems controlling essential bodily functions.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less
Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National ....Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National Research Priority 2: Promoting and Maintaining Good Health and especially to the sub-areas of this Research Priority 2: Ageing well, ageing productively and Preventative healthcare.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101807
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Fat sensing in the oral cavity and gastrointestinal tract: role in the regulation of gastrointestinal function and energy intake in health and obesity. This project will determine whether a reduced capacity to sense, or taste, the presence of fats in the oral cavity and the gastrointestinal tract diminishes the effects of fat on those aspects of gut function that regulate appetite and suppress energy intake. The project will, accordingly, provide important insights into the pathophysiology of ob ....Fat sensing in the oral cavity and gastrointestinal tract: role in the regulation of gastrointestinal function and energy intake in health and obesity. This project will determine whether a reduced capacity to sense, or taste, the presence of fats in the oral cavity and the gastrointestinal tract diminishes the effects of fat on those aspects of gut function that regulate appetite and suppress energy intake. The project will, accordingly, provide important insights into the pathophysiology of obesity.Read moreRead less
New mathematics for lipids and cells: structured models for atherosclerosis. The project aims to create new mathematical theory for immune cell behaviour which leads to heart attacks and strokes. This includes formulation and analysis of new types of mathematical models for atherosclerotic plaque development, leading to the creation of new mathematical tools to investigate cell fate in plaques and to generate new hypotheses for experimental research. Expected outcomes of this project include po ....New mathematics for lipids and cells: structured models for atherosclerosis. The project aims to create new mathematical theory for immune cell behaviour which leads to heart attacks and strokes. This includes formulation and analysis of new types of mathematical models for atherosclerotic plaque development, leading to the creation of new mathematical tools to investigate cell fate in plaques and to generate new hypotheses for experimental research. Expected outcomes of this project include powerful and reliable mathematical models ready for application, and national and international collaborations with scientists and mathematicians. This should provide significant benefits including increased capacity to use mathematical models in vascular biology and training young researchers in interdisciplinary methods.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100403
Funder
Australian Research Council
Funding Amount
$468,582.00
Summary
Defining how gut bacteria regulate metabolism: a role for gut serotonin. This project aims to understand how serotonin-producing cells in the gut interact with gut bacteria (the microbiome), using a combination of cells in culture and live germ-free and genetically modified mice. This project expects to generate new knowledge regarding cellular interactions that underlie important physiological pathways, such as the control of blood glucose and fat storage. The intended outcomes of this project ....Defining how gut bacteria regulate metabolism: a role for gut serotonin. This project aims to understand how serotonin-producing cells in the gut interact with gut bacteria (the microbiome), using a combination of cells in culture and live germ-free and genetically modified mice. This project expects to generate new knowledge regarding cellular interactions that underlie important physiological pathways, such as the control of blood glucose and fat storage. The intended outcomes of this project are to identify how gut bacteria communicate with serotonin-producing cells to regulate metabolism, and whether diet acts via a gut microbiome-serotonin axis to impact physiology. The expected benefit of this project will be to provide a new understanding of highly complex physiological systems that regulate our health.Read moreRead less
Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiol ....Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiology and molecular biology we expect to answer a fundamental question how STIM and Orai proteins interact to form functional store-operated calcium channels, and how the expression of STIM and Orai is regulated.Read moreRead less