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
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
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
Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. 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
The role of neurohormones in the regulation of appetite and successful sea water transfer in farmed Atlantic salmon. Cultured Atlantic salmon spend the first part of their life in freshwater and then following a physiological adaption phase called smoltification, the fish (now termed smolts) are transferred to sea cages for growout. A proportion of smolts fail to thrive after transfer, show slow or no growth and usually die some months later. This project will investigate the role that the neuro ....The role of neurohormones in the regulation of appetite and successful sea water transfer in farmed Atlantic salmon. Cultured Atlantic salmon spend the first part of their life in freshwater and then following a physiological adaption phase called smoltification, the fish (now termed smolts) are transferred to sea cages for growout. A proportion of smolts fail to thrive after transfer, show slow or no growth and usually die some months later. This project will investigate the role that the neurohomones that control both appetite and physiological stress in fish have in stimulating the resumption of feeding after sea water transfer.The basic knowledge generated will be used directly in development of strategies for minimising smolt failure in Atlantic salmon aquaculture.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
Urinary continence and incontinence in men: New insight through new technologies. Healthy ageing in men is largely overlooked. Disorders of continence are surprisingly common with increasing age, and are socially debilitating. To understand changes in continence and address healthy ageing it is first necessary to gain an understanding of continence mechanisms in healthy men. Continence in women has received wide attention, but anatomy and function differ, as do the challenges throughout life (ch ....Urinary continence and incontinence in men: New insight through new technologies. Healthy ageing in men is largely overlooked. Disorders of continence are surprisingly common with increasing age, and are socially debilitating. To understand changes in continence and address healthy ageing it is first necessary to gain an understanding of continence mechanisms in healthy men. Continence in women has received wide attention, but anatomy and function differ, as do the challenges throughout life (childbirth vs. prostate disease). Using novel methods we will test a new hypothesis of male continence with the goal to provide new physiological discoveries, new methods, and baseline data upon which strategies to enhance healthy ageing and reduce the economic burden of disorders of continence can be developed and refined. Read moreRead less
Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quali ....Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quality of life for older Australians and address the physical realities of an ageing workforce. Benefits extend to enhancing workplace safety and productivity, improving farming efficiencies for livestock and aquaculture industries, and training emerging leaders in the biological sciences.Read moreRead less