Novel therapies to limit renal fibrosis in diverse models of renal disease. Kidney failure is a devastating health, social and financial outcome for the individual, their employer, family and the broader society, This project will carefully dissect mechanisms underpinning the scarring in the kidney that predisposes to kidney failure and will investigate novel therapies to prevent kidney damage.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Phospholipids and kinases as regulators of epithelial sodium channels. The intracellular signalling pathways that will be identified in this project will facilitate the development of novel therapies for the many conditions in which the activity of epithelial sodium channels is abnormal. These include influenza, otitis media, high blood pressure and cystic fibrosis. It will also provide training for post-doctoral fellows and research students in a number of the key techniques in modern cellular ....Phospholipids and kinases as regulators of epithelial sodium channels. The intracellular signalling pathways that will be identified in this project will facilitate the development of novel therapies for the many conditions in which the activity of epithelial sodium channels is abnormal. These include influenza, otitis media, high blood pressure and cystic fibrosis. It will also provide training for post-doctoral fellows and research students in a number of the key techniques in modern cellular physiology.Read moreRead less
Indoleamine 2,3-dioxygenase-2: a newly discovered enzyme with a key role in kidney function. We have discovered an enzyme, IDO2, that metabolises the amino acid tryptophan. The enzyme is found in kidney tubule cells and we propose that IDO2 activity regulates sodium reabsorption by the renal tubular cells. Regulation of sodium balance is important for determining blood pressure in health and disease.
Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium conce ....Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium concentration, phosphorylation and membrane composition, and isolate its charge-transporting steps. The results will have immediate impact on the understanding of the enzyme's mechanism, its metabolic control and its role in disease.Read moreRead less
Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events inv ....Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events involved in controlling gene expression during development and differentiation. Results from this project will also provide new insights into the 'multifunctionality' of cellular proteins and will illustrate the importance of RNA studies in molecular medicine.Read moreRead less
Development of an electrode for stimulation of a transplanted neosphincter. This project aims to develop a novel electrode as an integral component of a new treatment for severe stress urinary incontinence. Treatments for severe stress urinary incontinence are associated with complications and are not completely effective. The new electrode is designed to be activated by an implanted stimulator to control an innervated smooth muscle graft (the neosphincter) to regulate the flow of urine from the ....Development of an electrode for stimulation of a transplanted neosphincter. This project aims to develop a novel electrode as an integral component of a new treatment for severe stress urinary incontinence. Treatments for severe stress urinary incontinence are associated with complications and are not completely effective. The new electrode is designed to be activated by an implanted stimulator to control an innervated smooth muscle graft (the neosphincter) to regulate the flow of urine from the bladder. Project research into the design of the electrode will focus on providing safe, effective and efficient stimulation of the neosphincter, while ensuring minimal damage to the surrounding tissues and affording straightforward implantation at surgery.Read moreRead less
Development of an electrode assembly for the stimulation of a transplanted innervated smooth muscle sphincter. This project will design and assess a number of different electrode designs for use in a medical device being developed for the treatment of severe stress urinary incontinence. The project will identify an optimal electrode design, which will be used in future clinical trials of the device.
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
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.