Computational Study Of Selectivity, Gating And Mutation In The Acetylcholine Receptor And Potassium Channels
Funder
National Health and Medical Research Council
Funding Amount
$301,393.00
Summary
One way cells in living organisms communicate with each other is via the passage of charged particles across the cell membrane. This takes place through ion channels, large protein molecules that span the membrane and allow small molecules or ions to pass through a central pore. Malfunction of ion channels is known to underlie a variety of disorders including epilepsy, hypertension, kidney disease, heart attack, deafness. Channels also provide promising targets for making new broad spectrum anti ....One way cells in living organisms communicate with each other is via the passage of charged particles across the cell membrane. This takes place through ion channels, large protein molecules that span the membrane and allow small molecules or ions to pass through a central pore. Malfunction of ion channels is known to underlie a variety of disorders including epilepsy, hypertension, kidney disease, heart attack, deafness. Channels also provide promising targets for making new broad spectrum antibiotics and antivirals. This project aims to study two important types of ion channel: acetylcholine receptors that convey signals between nerve and muscle cells, and potassium channels that regulate the nerve impulses themselves. The binding of the neurotransmitter acetylcholine released from a nerve cell to acetylcholine receptors in the muscle cell prompts the opening of a cation conductive pore. The resulting influx of ions initiates a cascade of events ending in the contraction of the muscle fibre. However, the way in which this channel opening is initiated and how ions move into the muscle cell remain to be determined. Potassium channels are primarily used to rapidly 'switch off' nerve impulses so that subsequent messages can be passed through the nerve cell. To do this they have to be highly discriminatory, allowing only potassium to pass across the cell membrane and not sodium that would initiate another impulse. Although we now know what these tiny proteins look like, it is not clear how they differentiate between types of ions while still allowing many millions to pass each second. We will use computer simulations to study how these two type of channel open and close, and how they discriminate between different ion types. Using sophisticated computational techniques on Australia's most powerful supercomputers we aim to elucidate this fundamental area of human biology in the hope of deriving treatments for some debilitating neuromuscular diseases.Read moreRead less
Investigation Of The Function Of The Scaffolding Protein LIN-2/CASK In Cholinergic Synapses
Funder
National Health and Medical Research Council
Funding Amount
$911,656.00
Summary
Scaffolding proteins play vital role in synapses to maintain the function of the nervous system. One important scaffolds LIN-2/CASK has been implicated in autism disorders and has profound effect on synaptic function. Here we investigate the function of LIN-2/CASK and its binding partners in cholinergic synapses to dissect how they regulate synaptic transmission.
Characterisation Of A Novel Human Neuromuscular Disease Associated With Deficiency Of The Syntrophins And Dystrobrevin.
Funder
National Health and Medical Research Council
Funding Amount
$284,069.00
Summary
The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affec ....The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affected babies are never able to breathe adequately, and die during the first weeks of life. No specific treatment is currently available. Until recently the underlying gene and protein abnormalities resulting in the majority of cases of muscular dystrophy were unknown and hence definitive diagnosis and prenatal diagnosis was not possible. We have recently identified deficiency of a group of muscle proteins, the syntrophins and dystrobrevin, in 15 children with severe weakness, in whom the cause was previously unknown. This group of patients represent the first examples of a novel neuromuscular disorder. We will now identify the disease-causing genetic mutations in these patients and determine how abnormalities in these muscle proteins lead to muscle weakness and degeneration. This research will have immediate application to clinical practice as we will be able to give the childrens' families accurate information about the risk to future offspring and offer prenatal diagnosis. In addition, it will provide new and important information concerning the normal function of human skeletal muscle, which can be used to develop therapies for affected patients.Read moreRead less
Tissue Engineering Skeletal Muscle – An Important Link In The Neuro-prosthetic Interface Of Bionic Limbs.
Funder
National Health and Medical Research Council
Funding Amount
$86,733.00
Summary
Limb loss after tumour, trauma, disease or degeneration is a major cause of disability. Use of a patient’s own nerve signals may offer an intuitive method for controlling a robotic limb to regain independence. Delicate nerves are damaged by the electrodes required for recording nerve signals, but muscles tolerate electrodes well. This project aims to create an artificial muscle construct as a bridge between nerve signals and recording electrodes to enable patient control of robotic limbs.
The Role Of Connexin40 In The Pathogenesis Of Atrial Fibrillation Probed By Targeted In Vivo Gene Transfer
Funder
National Health and Medical Research Council
Funding Amount
$529,015.00
Summary
Atrial fibrillation (AF) is a fast and irregular heart rhythm that can predispose sufferers to heart failure and stroke. AF occurs as the result of abnormal electrical conduction in the upper heart chambers. We have found that a protein called Cx40 causes abnormal conduction in heart cells when grown in culture. The aim of this research is to see if AF occurs when Cx40 is increased and prevented when Cx40 is decreased in an AF animal model, potentially defining Cx40 as new therapeutic target.