Molecular Interactions Of Novel Conotoxin Inhibitors Of The Noradrenaline Transporter
Funder
National Health and Medical Research Council
Funding Amount
$392,036.00
Summary
A novel class of conotoxins (chi-conotoxins) has been discovered in the venom of an Australian cone snails, Conus marmoreus. Chi-conotoxins are the first peptide inhibitors of the noradrenaline transporter. From binding studies, it appears they act at a new site, remote from the site of action of antidepressants. This project is aimed at understanding how and where this novel class of peptide binds to the transporter. The results of this study are designed to maximise the potential of these pate ....A novel class of conotoxins (chi-conotoxins) has been discovered in the venom of an Australian cone snails, Conus marmoreus. Chi-conotoxins are the first peptide inhibitors of the noradrenaline transporter. From binding studies, it appears they act at a new site, remote from the site of action of antidepressants. This project is aimed at understanding how and where this novel class of peptide binds to the transporter. The results of this study are designed to maximise the potential of these patented peptides to be used as leads to the development of a new class of therapeutic for controlling the adverse effects of inadequate noradrenaline balance.Read moreRead less
Airway Smooth Muscle Contribution To Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflamma ....Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflammation are linked to changes in the airway which include structural protein deposition - breakdown and an overgrowth of the smooth muscle that lines the walls of the airway. Our work is focussed on understanding the relationship between the structural protein deposition - breakdown and excess muscle growth. We also hope to gain a better understanding of the way asthma treatments combat these changes in the asthmatic airways.Read moreRead less
NADPH Oxidase In Pathological Angiogenesis In Solid Tumours And Retina
Funder
National Health and Medical Research Council
Funding Amount
$581,989.00
Summary
Understanding blood vessel growth has profound clinical implications for many diseases. Blocking vessel growth is a promising strategy for treatment of cancer and eye complications accompanying diabetes, whereas treatments to stimulate new vessel growth will treat ischemic disorders ie. heart attack and stroke. Here we investigate whether targeting an enzyme that grows blood vessels has potential for making drugs to stop tumor growth or eye damage that occurs with diabetes and premature births.
SPECIFIC MODIFICATION OF SKELETAL MUSCLE RYANODINE RECEPTOR ACTIVITY
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
The project will have implications for muscle fatigue, which is a public health issue in an aging population, and for neuromuscular diseases and muscle weakness. The ryanodine receptor (RyR) calcium release channel regulates changes in calcium concentrations inside the muscle cell that are essential for respiration and movement. Defects in expression of RyRs results in death in utero or at birth. The RyR is also important in many other tissues, where it acts either alone or in combination with a ....The project will have implications for muscle fatigue, which is a public health issue in an aging population, and for neuromuscular diseases and muscle weakness. The ryanodine receptor (RyR) calcium release channel regulates changes in calcium concentrations inside the muscle cell that are essential for respiration and movement. Defects in expression of RyRs results in death in utero or at birth. The RyR is also important in many other tissues, where it acts either alone or in combination with a second type of calcium channel, to regulate the changes in the concentrations of calcium ions within the cell, which are essential for a variety of processes including cardiac contraction, vascular constriction, neuronal activity and immune responses. Despite its importance, little is known about the regulation of the RyR channel opening during contraction in skeletal muscle or the mechanisms of ion movement through its pore. It is often difficult to define the specific role of RyRs in intact tissues because of the lack of specific probes for the channel. The RyR is an obvious target for therapeutic drugs to modify muscle contraction, but has not been used as such because of the lack of specific and reversible drugs. Muscle performance is reduced, and fatigue is rapid, in neuromuscular disease. Performance can be improved by variety of drugs like anabolic steroids which unfortunately have additional adverse actions. The aims of the project are (a) to discover more about the regulation of, and ion conduction pathway through, the skeletal muscle RyR channel, (b) to identify compounds that can be used as specific probes for RyR activity and (c) to identify compounds that might in the future provide the basis for development of the RyR as a therapeutic target.Read moreRead less