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
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.
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
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
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