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.
The critical role of kisspeptin/neurokinin/dynorphin (KNDy) neurons in gonadotropin releasing hormone (GnRH) release. The brain controls fertility through the secretion of its primary stimulatory factor, gonadotropin releasing hormone (GnRH). Brain cells producing three key peptide hormones, kisspeptin, neurokin B and dynorphin (termed KNDy cells) are vital for the control of GnRH. This project will detail the role of KNDy cells in puberty and reproduction.
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
Brain Regulation of Reproduction: Challenging the ‘KNDy’ Hypothesis. The brain switches reproduction on and off by changing the frequency of pulses of gonadotrophin releasing hormone. The processes that produce the pulses have been a puzzle for decades but, recently, brain cells that produce three peptides (kisspeptin, neurokinin B, dynorphin), known as ‘KNDy cells’, have been heralded as the ‘missing link’, or even the ‘pulse generator’. Using sheep, this project will challenge the KNDy hypothe ....Brain Regulation of Reproduction: Challenging the ‘KNDy’ Hypothesis. The brain switches reproduction on and off by changing the frequency of pulses of gonadotrophin releasing hormone. The processes that produce the pulses have been a puzzle for decades but, recently, brain cells that produce three peptides (kisspeptin, neurokinin B, dynorphin), known as ‘KNDy cells’, have been heralded as the ‘missing link’, or even the ‘pulse generator’. Using sheep, this project will challenge the KNDy hypothesis with pheromones and with acute increases in nutrition, two factors that rapidly increase the frequency of gonadotrophin releasing hormone pulses. The outcomes of this research are directly relevant to the optimisation of reproductive management in farm animals, wildlife and humans.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
Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregul ....Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregulation of the IGF system has been implicated including cancer, diabetes and atherosclerosis.
Since IGFs are major determinants of growth, the outcomes of this project could also lead to improvements in animal production with major benefit to primary industry. New IGF analogues developed could assist biotechnology exports.
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Non-classical steroid signalling through SF-1 responsive genes: a key mechanism in environmental endocrine disruption, cancer, and aging. Endocrine disruption by pervasive manmade chemicals, which mimic natural hormones, and are found in plastics, cosmetics, and fire retardants, is known to cause developmental defects in model organisms and wildlife, with substantial risk also to human health. This risk increases with increasing population density and dependence on water recycling. Current tests ....Non-classical steroid signalling through SF-1 responsive genes: a key mechanism in environmental endocrine disruption, cancer, and aging. Endocrine disruption by pervasive manmade chemicals, which mimic natural hormones, and are found in plastics, cosmetics, and fire retardants, is known to cause developmental defects in model organisms and wildlife, with substantial risk also to human health. This risk increases with increasing population density and dependence on water recycling. Current tests to assess such substances use oversimplified modes of hormone action and grossly underestimate the risk of endocrine disruption. This proposal will yield new knowledge about how such substances act in the body, or on wildlife, and form the basis for new more sensitive methods of environmental monitoring.Read moreRead less
New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways res ....New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways responsible for how a cell manages stress by regulating levels of proteins involved in the cellular stress response. Discoveries made during the course of this research will provide knowledge of gene and protein interactions that will be important in the future to develop anti-cancer therapies. Read moreRead less
Proteolysis of binding protein complexes regulates bioavailability of insulin-like growth factor (IGF). We aim to determine how growth factors kept inactive in complexes in the blood can become free and active. The fundamental knowledge gained will help us understand the regulation of growth factors' availability to tissues and develop novel or more effective delivery systems for therapeutic growth factors that could impact on several conditions including diabetes, growth disorders and critical ....Proteolysis of binding protein complexes regulates bioavailability of insulin-like growth factor (IGF). We aim to determine how growth factors kept inactive in complexes in the blood can become free and active. The fundamental knowledge gained will help us understand the regulation of growth factors' availability to tissues and develop novel or more effective delivery systems for therapeutic growth factors that could impact on several conditions including diabetes, growth disorders and critical illness. This project therefore benefits Australia at two levels: by maintaining our international leadership in the study of these important growth-regulatory molecules, and by providing a better understanding of physiological mechanisms that might benefit the health of Australians and provide opportunities to develop novel therapeutics.Read moreRead less