Mitochondrial L-arginine Transport And Its Role In The Pathogenesis Of Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$525,660.00
Summary
Heart failure is a common disorder that is marked by significant symptoms and reduced survival. Reduced cardiac performance is the key responsible mechanism. At the tissue level, altered energy metabolism is a major contributor. Mitochondria are the cellular elements that produce energy and in this project we aim to study how a key process that regulates mitochondrial activity behaves in the setting of heart failure.
The PDZ Scaffold NHERF-1; A Novel Regulator Of Astrocyte Function?
Funder
National Health and Medical Research Council
Funding Amount
$444,500.00
Summary
Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astr ....Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astrocyte membranes where the particular biological job has to be performed. How are they targeted to, and retained in these places? We have preliminary data suggesting that a specialised protein called NHERF-1, can bind a group of these proteins, called glutamate transporters, thereby anchoring them to the skeleton of the cell. If we are correct then we should be able to manipulate this interaction, both in live brain tissues, and in simple cell culture systems, using a variety of physiological and molecular biology techniques. If we are correct in our hypothesis, then our findings will have immense value in trying to reduce damage that occurs in human brains in conditions such as strokes, where a breakdown in the control of glutamate around neurons causes extensive and irreversible brain damage.Read moreRead less
Molecular Mechanism And Novel Activators Of Amino Acid And Calcium-sensing Class 3 G-protein Coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
When we eat protein-containing foods, our bodies extract twenty different amino acids for growth and tissue regeneration. Broad-spectrum amino acid sensing receptors detect the increases in blood amino acid levels and respond by triggering the release of biochemical signals. This project will establish the molecular rules by which these receptors work and identify novel activators with potential therapeutic application for the control of growth, tissue regeneration and calcium metabolism.
The Cystine Glutamate Antiporter And Classical Glutamate Transporters In Normal And Pathological Brains And Retinae
Funder
National Health and Medical Research Council
Funding Amount
$416,000.00
Summary
This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction ....This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction of action and release glutamate. The current study investigates a transport system (called the cystine-glutamate antiporter) where the normal direction of action is to release glutamate. This system has been overlooked despite evidence that it could be involved in releasing glutamate and thus contribute to the death of nerve cells in a variety of human pathologies including glaucoma of the eye, epilepsy, and brain damage that occurs when the blood supply to the brain is interrupted, such as after a heart attack. This study examines both human tissues and animal models of disease states to determine if similar transport systems are present and if the cystine-glutamate antiporter might contribute to human nervous diseases. The function and distribution of the cystine-glutamate antiporter will be compared with classical transporters, under normal and pathological conditions, including situations where we have shown that it is possible to experimentally perturb normal glutamate transporter expression.Read moreRead less
Proteins form up to 25% of our diet. The first step in protein absorption is the digestion of protein into smaller units called peptides and amino acids. Both components are subsequently taken up by specialised cells in the wall of the intestine. In this project we plan to study how protein absorption occurs at the surface of these intestinal cells and investigate why this process fails in malabsorption syndromes, where the uptake of amino acids is impaired.
A Novel Marker Of Distressed Neurons In The Hypoxic Brain: Regulation, Function And Potential Clinical Utility.
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
The brain is easily damaged by lack of oxygen (hypoxia). We have recently identified a novel protein called GLAST1b which is expressed in distressed neurons. This protein is a glutamate transporter. Glutamate is implicated as a toxic agent hypoxia. This study will investigate what regulates the expression of GLAST1b, what the consequences of expression are, and whether this marker can be developed as a diagnostic tool for identifying the presence of, and distribution of brain damage.