A Novel Approach To Streamlining The Diagnosis Of Primary Aldosteronism
Funder
National Health and Medical Research Council
Funding Amount
$269,463.00
Summary
This study will assess a new clinical test used to diagnose a potentially curable form of high blood pressure called primary aldosteronism (PA). If successful, the test will greatly streamline and simplify the diagnosis of this condition, with the potential for enormous cost savings and a markedly increased rate of diagnosis of patients with PA who can then benefit from optimal treatment and improved quality of life.
Elucidating Genetic Mechanisms Responsible For Familial Hyperaldosteronism Type II
Funder
National Health and Medical Research Council
Funding Amount
$424,812.00
Summary
Primary aldosteronism (PAL) is the commonest specifically treatable and potentially curable form of hypertension (high blood pressure), a common disease, expensive to treat, with serious morbidity and mortality. This project will use cutting edge technology to gain new knowledge concerning how genes regulate the body's production of aldosterone (salt hormone), which will help us understand how PAL develops and how common it is, and could lead to better approaches to diagnosis and treatment.
Interactions Between Vasoactive, Epigenetic And Immunogenic Pathways In The Development Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
In our community, diabetic retinopathy is the leading cause of vision loss in people of working age. As the prevalence of diabetic retinopathy increases, there is an urgent need to understand the factors that cause its development in order to develop new treatments. This proposal will explore the contribution of hormones, the memory of retinal cells to high glucose and stress, and the immune system to diabetic retinopathy. The goal is to develop new and improved treatments for Australians.
Understanding Vasoactive Hormone Pathways In Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$453,750.00
Summary
High blood pressure damages tissues. In clinical practice blood pressure is measured in large arteries, such as the brachial artery in the arm. However, it is the pressure within the organ such as the kidney that actually causes the damage. In particular, the sieving apparatus of the kidney (called the glomerulus), is especially sensitive to the effects of pressure. In diabetes, the pressure within the glomerulus is high because its outflow valve (called the efferent arteriole) is tightly constr ....High blood pressure damages tissues. In clinical practice blood pressure is measured in large arteries, such as the brachial artery in the arm. However, it is the pressure within the organ such as the kidney that actually causes the damage. In particular, the sieving apparatus of the kidney (called the glomerulus), is especially sensitive to the effects of pressure. In diabetes, the pressure within the glomerulus is high because its outflow valve (called the efferent arteriole) is tightly constricted. Therefore even if blood pressure is thought to be normal when measured in the arm, it may still be excessively high within the kidney. Studies have already shown that lowering within-kidney pressure may have a major impact on the progression of kidney disease in diabetes. However, to date this reduction of within-kidney pressure has been sub-maximal. The planned studies will involve the use of new compounds which have more powerful effects in reducing the formation or action of hormones which promote constriction of vessels in the kidney leading to elevated pressure within the kidney. Furthermore, some of these very new agents can open up or dilate these kidney vessels thereby achieving excellent reductions in the pressure inside the kidney. The proposed studies aim to examine new strategies for preferentially lowering pressure within the kidney down to these ideal levels. These hormones also have other effects which could be relevant to non-kidney sites of injury in diabetes including blood vessels and the retina.Read moreRead less
Mineralocorticoid Receptor Blockade: Mechanisms Of Selectivity
Funder
National Health and Medical Research Council
Funding Amount
$540,270.00
Summary
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in specific tissues.
Factors Regulating The Temporal And Spatial Assembly Of G-protein Coupled Receptor-mediated Arrestin Complexes
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
G-protein coupled receptors are proteins that are present at the surface of most cells in the human body. They recognise and bind to specific molecules, such as hormones, the act of which results in a specific signal being transmitted into the cell. This signal alters the function of the cell and so it is critical that it is appropriate, both in type and duration. G-protein coupled receptors and the molecules that activate them provide an essential function within the human body for communicatin ....G-protein coupled receptors are proteins that are present at the surface of most cells in the human body. They recognise and bind to specific molecules, such as hormones, the act of which results in a specific signal being transmitted into the cell. This signal alters the function of the cell and so it is critical that it is appropriate, both in type and duration. G-protein coupled receptors and the molecules that activate them provide an essential function within the human body for communicating between cells, and consequently between organs. They are a major mechanism by which nerve signals are transmitted and hormones regulate bodily functions. They are therefore an important target for pharmaceuticals, with up to 50% of ethical drugs and many drugs of abuse acting upon them. It is critical to understand how these receptors alter cellular function once they receive an appropriate signal, but it is also essential to know how such responses are switched off. Arrestins are proteins within cells that interact with G-protein coupled receptors to 'arrest' their signalling. They desensitise the cell to continuous stimulation, but also act to resensitise the cell to respond to future, separate signals. Recently, they have also been shown to provide alternative mechanisms of altering cellular activity by interacting with other cellular proteins. These interactions greatly increase the potential ways in which a cell can respond once a G-protein coupled receptor is activated. Understanding the resulting complexity is essential if we are to fully exploit the vast therapeutic potential of this important receptor family.Read moreRead less
An obesity epidemic is evident in first world countries including Australia. Twenty seven percent of men aged 55-64 in this country are obese. Obesity results in increased mortality and morbidity from type 2 diabetes, cardiovascular disease, renal disease and endometrial cancer, among others. Given our flaccid lifestyles, it is imperative that the metabolic processes underlying obesity be fully understood, to allow development of suitable treatment modalities. This proposal seeks to establish an ....An obesity epidemic is evident in first world countries including Australia. Twenty seven percent of men aged 55-64 in this country are obese. Obesity results in increased mortality and morbidity from type 2 diabetes, cardiovascular disease, renal disease and endometrial cancer, among others. Given our flaccid lifestyles, it is imperative that the metabolic processes underlying obesity be fully understood, to allow development of suitable treatment modalities. This proposal seeks to establish an important new element in our understanding of the development of obesity, the transcription factor STAT5. With previous NHMRC support, we developed sophisticated genetically modified mice which lack defined signalling processes initiated by growth hormone, an anti-obesity agent. These studies showed a strong correlation between ability to activate STAT5 and resistance to obesity. There is fragmentary literature evidence to support our hypothesis, which could also explain some of leptins anti-obesity actions. Using mice which lack STAT5, we shall establish a role for STAT5 as an antiobesity agent. The actions of STAT5 are normally blocked by feedback inhibitors referred to as SOCS, discovered by Australians. We shall define which SOCS is the feedback regulator for obesity control, allowing us to develop specific anti-SOCS agents which will act as novel anti-obesity agents.Read moreRead less