Ultrasound in muscle vascular research, and gene therapy. This project focuses on ultrasound and microbubbles for the imaging of microvascular blood flow patterns in skeletal muscle and as a modality for drug delivery. The aim is to develop and refine technology specifically for (i) assessment of muscle microvascular flow in health and disease, and for (ii) delivery of state-of-the art gene constructs to endothelial cells that control blood flow in the muscle microvasculature. We anticipate impr ....Ultrasound in muscle vascular research, and gene therapy. This project focuses on ultrasound and microbubbles for the imaging of microvascular blood flow patterns in skeletal muscle and as a modality for drug delivery. The aim is to develop and refine technology specifically for (i) assessment of muscle microvascular flow in health and disease, and for (ii) delivery of state-of-the art gene constructs to endothelial cells that control blood flow in the muscle microvasculature. We anticipate improved technology for early diagnosis of impairment in microvascular flow relevant to muscle insulin resistance and novel therapeutics that improve muscle microvascular blood flow applicable to the treatment of diabetes.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
Blood flow routes in muscle. Ageing well, ageing productively. The Australian population is ageing. The proportion of the population over the age of 65 is expected to greatly increase, reaching 22% by the year 2030. The prevalence of type 2 diabetes in this older population is thought to be ~20%, compared to ~6% in younger populations. An initial cause of type 2 diabetes may be microvascular dysfunction brought on by physical inactivity. Therefore this project addresses the concepts of microvasc ....Blood flow routes in muscle. Ageing well, ageing productively. The Australian population is ageing. The proportion of the population over the age of 65 is expected to greatly increase, reaching 22% by the year 2030. The prevalence of type 2 diabetes in this older population is thought to be ~20%, compared to ~6% in younger populations. An initial cause of type 2 diabetes may be microvascular dysfunction brought on by physical inactivity. Therefore this project addresses the concepts of microvascular function and microvascular fitness by using the latest technology to map blood flow routes in muscle under a number of relevant situations. Read moreRead less
Microdialysis for monitoring changes in microvascular flow patterns in muscle. Microdialysis is a technique for sampling interstitial fluid. Factors altering vascular delivery and removal of nutrients and hormones can affect muscle metabolism by altering exchange with the interstitium. This project focuses on microdialysis for assessing the impact of microvascular blood flow patterns on skeletal muscle metabolism and contractility. The aim is to develop and refine the technology, including equat ....Microdialysis for monitoring changes in microvascular flow patterns in muscle. Microdialysis is a technique for sampling interstitial fluid. Factors altering vascular delivery and removal of nutrients and hormones can affect muscle metabolism by altering exchange with the interstitium. This project focuses on microdialysis for assessing the impact of microvascular blood flow patterns on skeletal muscle metabolism and contractility. The aim is to develop and refine the technology, including equations, specifically for monitoring the nutritive fraction of blood flow in muscle by agents and factors relating to health and disease. This technique could be used for screening drugs in the treatment of diseases such as type 2 diabetes and related conditions.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
Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 defici ....Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 deficient animals are 40 percent larger than normal. Consequently, we wish to determine how SOCS-2 acts to limit the size of an animal and whether this involves regulation of growth hormone action.Read moreRead less
Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control h ....Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control holistic physiological responses is largely unknown. By deciphering how neural networks are formed this project aims to provide broad biological insight to wiring of the entire nervous system which is likely to have significant implications for the formation of synthetic neural networks and for regeneration.Read moreRead less
Establishment of the endocrine axes in the embryo and their xenobiotic distortion. Millions of tons of supposedly harmless chemicals are produced and enter the environment each year. However, some of these substances can act on wildlife and humans to distort the way that hormone systems are established in the embryo, leading to subtle effects on health and function in later life. We will use one of the commonest of these substances, found in many cosmetics, food wrappings, and medicinal plastics ....Establishment of the endocrine axes in the embryo and their xenobiotic distortion. Millions of tons of supposedly harmless chemicals are produced and enter the environment each year. However, some of these substances can act on wildlife and humans to distort the way that hormone systems are established in the embryo, leading to subtle effects on health and function in later life. We will use one of the commonest of these substances, found in many cosmetics, food wrappings, and medicinal plastics, to learn how hormone systems becomes established in a healthy embryo, and how these then get distorted after exposure to these compounds. This project directly addresses the way we assess the health of our environment, and offers ways to screen for compounds which can have subtle effects on wildlife, domestic species and humans.Read moreRead less
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less