The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic c ....The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic cell recirculation, and what consequences the recirculation has for immune cell function. This understanding will significantly advance our basic understanding of the immune system.Read moreRead less
Saving your skin: physiology of immune regulation in mammalian lymph nodes. The overall aim of this proposal is to understand the mechanisms through which a rare population of regulatory cells maintains skin integrity. Despite their importance, little is known about the regulatory pathways these cells utilise. Previous work from the team has described an innovative technique to enrich these cells for in-depth study and demonstrated their potent regulatory capacity in vivo. This project will enha ....Saving your skin: physiology of immune regulation in mammalian lymph nodes. The overall aim of this proposal is to understand the mechanisms through which a rare population of regulatory cells maintains skin integrity. Despite their importance, little is known about the regulatory pathways these cells utilise. Previous work from the team has described an innovative technique to enrich these cells for in-depth study and demonstrated their potent regulatory capacity in vivo. This project will enhance our understanding of these cells and uncover their mechanisms of action. The outcomes of this work will therefore provide fundamental new knowledge of skin physiology, and lead to novel insights regarding how healthy skin, which is essential for the very survival and function of a living organism, may be maintained.Read moreRead less
Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated w ....Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated with painful and often lethal co-morbidities.Read moreRead less
Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of ....Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of productivity, and paralleled decline in the resident macrophages in these organs may be a common ageing mechanism. Demonstration that altered macrophage biology unpins decline in blood and bone may prolong peak health and increase productivity in the ageing population.Read moreRead less
How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the ....How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the activation of this system to trigger the local generation of AngII. This project addresses the question of where exactly in the heart the RAS components are turned on, how they interact to generate AngII and whether the activation of the local RAS is beneficial or not to cardiac function. The findings should provide critical insights into an important hormonal system.Read moreRead less
Neural circuits that mediate fear conditioning and extinction. Understanding of how the brain processes, stores and retrieves information and produces behavioural outcomes is in its infancy. This project will use electrophysiology and molecular techniques to understand the circuits that mediate one form of emotional learning.
Discovery Early Career Researcher Award - Grant ID: DE140100135
Funder
Australian Research Council
Funding Amount
$395,199.00
Summary
Understanding equine incretins: a novel approach to laminitis prevention. Laminitis is a crippling foot disease in horses which incurs significant economic and social costs. Recent studies have shown that persistently high insulin concentrations can trigger laminitis, and that high insulin levels are caused by the excessive release of hormones called incretins. This project aims to determine the role of incretins and their receptors in causing abnormal equine insulin secretion. The distribution ....Understanding equine incretins: a novel approach to laminitis prevention. Laminitis is a crippling foot disease in horses which incurs significant economic and social costs. Recent studies have shown that persistently high insulin concentrations can trigger laminitis, and that high insulin levels are caused by the excessive release of hormones called incretins. This project aims to determine the role of incretins and their receptors in causing abnormal equine insulin secretion. The distribution of equine incretin receptors will be described for the first time, and the consequences of incretin receptor binding will be characterised. Understanding equine incretin biology may lead to novel therapies for laminitis.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
Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM re ....Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM remodelling. Previous studies have developed a unique mouse model of childhood asthma and discovered the molecular mechanism by which this tissue tropism develops in response to virus infection. This project will identify new targets for immunomodulation and design new biologics to block ASM remodelling and the deleterious effects of respiratory virus infection in asthmatic subjects. Read moreRead less
The role of muscle and tendon mechanics in human muscle damage. This project aims to examine what sort of forceful stretch is required to cause exercise induced muscle damage (EIMD) in humans and how muscles adapt to limit future damage. Specifically, the project aims to examine how the elastic properties of tendons might reduce muscle damage by buffering stretch in muscle fibres. Using cutting-edge ultrasound imaging technology, human muscle strain in different regions of muscle will be examine ....The role of muscle and tendon mechanics in human muscle damage. This project aims to examine what sort of forceful stretch is required to cause exercise induced muscle damage (EIMD) in humans and how muscles adapt to limit future damage. Specifically, the project aims to examine how the elastic properties of tendons might reduce muscle damage by buffering stretch in muscle fibres. Using cutting-edge ultrasound imaging technology, human muscle strain in different regions of muscle will be examined to quantify the temporal relationship between muscle power absorption and EIMD. The importance of muscle and tendon mechanical properties in buffering the muscle from potential damage will be gauged. This could be a critical mechanism for preventing EIMD in exercising humans.Read moreRead less