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
Masterminding Reproduction: Kisspeptin and RFamide-Related Peptide. There are a number of concerning trends in reproductive health. Women are reporting difficulty conceiving and maintaining pregnancies; while sperm count and quality are declining in men. More concerning is the increase in reproductive cancers. Gonadotropin-releasing hormone (GnRH) antagonist and agonist have been used for decades to treat reproductive cancers (such as breast cancer and prostate cancer), infertility and precociou ....Masterminding Reproduction: Kisspeptin and RFamide-Related Peptide. There are a number of concerning trends in reproductive health. Women are reporting difficulty conceiving and maintaining pregnancies; while sperm count and quality are declining in men. More concerning is the increase in reproductive cancers. Gonadotropin-releasing hormone (GnRH) antagonist and agonist have been used for decades to treat reproductive cancers (such as breast cancer and prostate cancer), infertility and precocious puberty. Kisspeptin and RF-related peptide may offer more physiological alternatives to GnRH, without detrimental side effects. We will fully explore these two newly defined and major players in reproduction and provide a physiological framework for their progression to clinical use.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883078
Funder
Australian Research Council
Funding Amount
$356,000.00
Summary
Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell bio ....Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell biology and for underpinning commercial developments of new molecular targets for therapeutic drugs for many diseases including cancer, cardiovascular disease and reproductive disorders. This facility is pivotal to maintaining international competitiveness in many areas of biological research in national priority areas.Read moreRead less
Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the ....Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the Golgi remain largely unknown. We have recently cloned a novel ATP-binding protein specifically expressed at the Golgi apparatus in human brain, and hypothesise that this protein regulates Golgi protein trafficking by interacting with two other molecules, dynamin and calcium, during cell secretion.Read moreRead less
Insulin-like growth factor binding proteins: structure and ligand interactions. Insulin-like growth factors are important for normal growth and development. Their actions are regulated by a family of IGF binding proteins. In order to understand the mechanism of this regulation, the aim of this project is to determine the 3-dimensional structure of 2 IGFBPs in complex with IGFs. This will lead to a comprehensive understanding of this interaction that promises to provide important basic knowledge ....Insulin-like growth factor binding proteins: structure and ligand interactions. Insulin-like growth factors are important for normal growth and development. Their actions are regulated by a family of IGF binding proteins. In order to understand the mechanism of this regulation, the aim of this project is to determine the 3-dimensional structure of 2 IGFBPs in complex with IGFs. This will lead to a comprehensive understanding of this interaction that promises to provide important basic knowledge as well as having major implications for biotechnology, agriculture and health.Read moreRead less
The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present a ....The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present an opportunity to control hypertension whilst simultaneously limiting fibrosis in the kidney. Renal failure is steadily increasing and is now the single largest health care cost to the community. These studies will provide the proof of concept required to ultimately bring this novel preventative therapy to the community.Read moreRead less
Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity ....Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity, insulin resistance and various forms of cancers is well established) are leading to a rapid increase in new cancer cases, thus driving a rapid increase in demand for better treatments. This is particularly relevant in Indigenous health where obesity is on the rise following the transition from a traditional to an urban lifestyle.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100191
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
An advanced mass spectrometer for applications in phospho-proteomics, glycomics and top-down sequencing of proteins. This cutting-edge mass spectrometry facility will benefit the Hunter Valley research community comprising 100 researchers in this field. It will enable the researchers to enhance their research productivity in areas of national importance, including better understanding the etiology of disease states, reproductive health and the regulation of plant growth.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100203
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
Accessing the third dimension in scanning electron microscopy for rapid, high resolution tomography of large samples. Understanding the three-dimensional structure of materials is essential for modern research. This facility will allow rapid three-dimensional imaging of materials within a scanning electron microscope, including sustainable polymers, tissues from plants and nanocomposites. This will enable high-quality research in science, engineering and medicine.