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
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
Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. Th ....Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. The pioneering work carried out on Acropora in this laboratory suggests that it is perhaps the best choice currently available for this purpose. This project will use Acropora to address fundamental questions about the evolution of nervous system developmental processes.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
Hydrogel systems for effective encapsulation of functional pancreatic islet cells. This proposal addresses the problem of maintaining viability and function of cells encapsulated within an immuno-isolation barrier material. The research will develop biosynthetic materials that are able to meet design criteria for an effective biomaterial for this application. The major benefits to Australia will be in improved health outcomes by providing safer, more efficacious materials, economic growth develo ....Hydrogel systems for effective encapsulation of functional pancreatic islet cells. This proposal addresses the problem of maintaining viability and function of cells encapsulated within an immuno-isolation barrier material. The research will develop biosynthetic materials that are able to meet design criteria for an effective biomaterial for this application. The major benefits to Australia will be in improved health outcomes by providing safer, more efficacious materials, economic growth development of the Australian Medical Device industry and in high level training of researchers in this field.Read moreRead less
Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular b ....Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in this complex process.Read moreRead less
Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's exist ....Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's existing strength in cell biology and neuroscience and provide high quality training for an undergraduate student and post-doctoral scientist.Read moreRead less