The L-type Calcium Channel In Cardiovascular Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Calcium influx into cardiac muscle cells occurs via the L-type calcium channel. The channel is essential to life but when function is altered it can contribute to the development of sudden death and heart failure. I have made significant discoveries in understanding the role of the channel in disease and I have exploited this knowledge to design therapy including a novel class of calcium channel antagonists to prevent the development of heart failure.
Venoms To Drugs: Translating Venom Peptides Into Human Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Many disorders of the nervous system, including chronic pain, epilepsy and the neuronal degeneration suffered following a stroke, result from malfunction of channels that ferry ions across neuronal cell membranes. There are very few drugs available for treating these disorders and they often have debilitating side-effects. We are developing potent and selective modulators of these ion channels as the next-generation of safe and effective analgesic, anti-epileptic, and neuroprotective drugs.
Despite dramatic improvements in diagnosis, prevention and treatment of heart disease, cardiovascular disease remains the commonest cause of death in Australia. The continuing decline in mortality from ischaemic heart disease has been offset by an increase in the incidence of sudden cardiac death due to abnormal heart rhythms. By understanding the basic mechanisms underlying cardiac arrhythmias we are seeking to develop more effective therapies to treat and/or prevent sudden cardiac death.
Mechanotransduction is defined as the ability of living cells to respond to and convert mechanical stimuli into electro-chemical cellular signals to ensure survival. It is largely dependent on membrane proteins known as mechanosensitive (MS) ion channels. These channels are involved in senses of hearing and touch, and are also crucial regulators of heart and muscle function. This research aims to elucidate the general physical principles underlying mechanotransduction in living cells.
The aim of this application is to find new therapeutic strategies for genetic epilepsy. "Disease in a dish" models as well as whole animal models will be generated that contain patient gene mutations and the underlying disease processes will be characterised. Using these models a range of existing and new drugs will be tested to select those that most completely reverse these disease processes. These results will feed into clinical trials in patients with appropriate genetic profiles.
Ion channels are molecular pores of excitable membranes facilitating passage of ions and organic solutes across cellular membranes. An ever-increasing number of human and animal diseases result from malfunctioning ion channels making them to important therapeutic targets, which are modulated by a range of currently prescribed drugs. In the recent years the scientific and medical community has become increasingly aware of the role that mechanosensitive ion channels play in pathology of diseases i ....Ion channels are molecular pores of excitable membranes facilitating passage of ions and organic solutes across cellular membranes. An ever-increasing number of human and animal diseases result from malfunctioning ion channels making them to important therapeutic targets, which are modulated by a range of currently prescribed drugs. In the recent years the scientific and medical community has become increasingly aware of the role that mechanosensitive ion channels play in pathology of diseases including cardiac hyperthrophy and arrhythmias.Read moreRead less
Molecular Mechanisms And Pharmacology Of The Dynamins
Funder
National Health and Medical Research Council
Funding Amount
$883,375.00
Summary
His research focuses on the molecular mechanisms of synaptic transmission in the nervous system to: a) understand the basic science of nerve communication and b) develop drugs to control diseases of nerve terminals like epilepsy. The main focus is on proteins called the dynamins, which are self-assembling molecular machines acting in many intracellular functions. There are three dynamin genes: dynI, II and III with diverse functions in the different parts of the body.
Venoms To Drugs: Translating Venom Peptides Into Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$751,854.00
Summary
Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treating chronic pain and many have significant side-effects. Several ion channels are critical for conducting pain signals to the brain. Blocking these channels can provide pain relief and, in some cases, protection from brain injury following stroke. We are producing potent and selective blockers of these ion channels for the treatment of chronic pain and strok ....Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treating chronic pain and many have significant side-effects. Several ion channels are critical for conducting pain signals to the brain. Blocking these channels can provide pain relief and, in some cases, protection from brain injury following stroke. We are producing potent and selective blockers of these ion channels for the treatment of chronic pain and stroke.Read moreRead less
Peripheral Membrane Proteins In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Peripheral membrane proteins are critical for processes such as cell transport, signaling, neurosecretion and development. As such, their dysfunction can lead to many debilitating diseases including cancer, inflammation and neurodegeneration. This project will establish fundamental new knowledge about how peripheral membrane proteins regulate cell function, how their perturbation or mutation results in human disease, and will inform efforts to target them for future therapeutic outcomes.
Developing Novel Neuroreceptor And Channel Therapies For Pain And Addiction
Funder
National Health and Medical Research Council
Funding Amount
$808,375.00
Summary
Chronic pain is a growing and poorly treated global health burden. There is a great need for novel pain therapeutics. We are discovering novel drug targets in pain pathways in the nervous system and new therapeutic molecules that selectively block information flow in pain nerves. Strong pain relieving drugs like morphine also lose their effectiveness after long periods of use. We are finding mechanisms responsible for this thereby providing a rational basis for development of better opioids and ....Chronic pain is a growing and poorly treated global health burden. There is a great need for novel pain therapeutics. We are discovering novel drug targets in pain pathways in the nervous system and new therapeutic molecules that selectively block information flow in pain nerves. Strong pain relieving drugs like morphine also lose their effectiveness after long periods of use. We are finding mechanisms responsible for this thereby providing a rational basis for development of better opioids and pain treatments.Read moreRead less