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Oxidative Regulation Of The Na Pump- A New Player In Vascular Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$504,427.00
Summary
Oxidative stress is a major player in hypertension, atherosclerosis, diabetes and ageing, but we have struggled to develop a therapy to successfully combat in heart and vascular cells in large clinical trials. We have discovered a new role for membrane protein FXYD1, to protect key heart and vascular proteins from functional impairment secondary to oxidative stress. We will investigate its role in protecting against vascular disease, and test novel therapies based on this endogenous protector.
Physiological Function Of Nedd4-2 In Regulating The Epithelial Sodium Channel And Cystic Fibrosis Transmembrane Conductance Regulator
Funder
National Health and Medical Research Council
Funding Amount
$949,572.00
Summary
Optimal transport of sodium and chloride ions is essential for the maintenance of electrolyte balance, blood volume, blood pressure and lung function. We are studying the control of a key sodium channel (the epithelial sodium channel) and a key chloride channel (cystic fibrosis transmembrane conductance regulator) by an enzyme called Nedd4-2. This project will enable us to understand how Nedd4-2 regulates these two ion channels and to study the pathological consequences of the loss of Nedd4-2.
Dynamic Action Potential Clamp Studies Of Drugs That Affect The Cardiac Action Potential
Funder
National Health and Medical Research Council
Funding Amount
$343,976.00
Summary
The development of drugs to treat and.or prevent cardiac arrhythmias have been plagued by the side-effect of actually increasing the risk of sudden death. One of the reasons for this is that drugs that work well in one part of the heart may cause problems in another part. We are developing a system called “dynamic action potential clamp” that will make it easier for researchers to assess the effect of drugs in different regions of both normal and diseased hearts.
Role Of Calcium-activated Potassium Channels In Neuronal Excitability, Synaptic Plasticity And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$612,272.00
Summary
Disturbances in brain function, as occur in diseases such as epilepsy and schizophrenia, are associated with abnormal electrical activity. This electrical activity leads to increases in calcium inside nerve cells. In this project we plan to investigate how changes in calcium inside nerve cells regulates electrical activity, and how this impacts on the capacity of the brain to process and learn new information.
Failure-to-progress In Human Labour Results From A Profound Electrical Negativity Of The Uterine Cells: Targeting The Ion Channels Involved
Funder
National Health and Medical Research Council
Funding Amount
$564,541.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems to lay the foundations for better therapeutics.
Interactions Between H5N1 And The Respiratory Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$623,065.00
Summary
This project examines the hypothesis that the severity of H5N1 infection is due to activation of signalling pathways in the lung not activated by human influenza and leads to fluid accumulation in the lungs death of respiratory cells. This study will improve our understanding of influenza infection and identify targets for treatment of H5N1.
Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
A Novel Therapeutic Target For Preventing Helicobacter Pylori-associated Diseases
Funder
National Health and Medical Research Council
Funding Amount
$750,336.00
Summary
Gastric cancer mainly results from chronic inflammation (gastritis) caused by the stomach-dwelling bacterium, Helicobacter pylori. We have identified a potassium channel which our data suggest could be a new therapeutic target for protecting against gastric cancer caused by H. pylori infection. This project will test the role of this channel in H. pylori gastritis and see whether drugs that target this channel can protect mice against H. pylori-associated disease.
Novel Analgesic Approaches: Harnessing Functional Interactions Between Sodium Channels And Opioids
Funder
National Health and Medical Research Council
Funding Amount
$329,076.00
Summary
Chronic pain is a debilitating condition that affects the life of one five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered that combination treatment with opioids and a novel venom-derived compound discovered by us provides effective pain relief. The aim of this project is to understand the mechanisms underlying this synergistic effect to develop new treatment approaches for pain.
Overcoming The Delivery Hurdle For Peptide Therapeutics: New Treatment For Autoimmune Diseases
Funder
National Health and Medical Research Council
Funding Amount
$574,955.00
Summary
Peptide blockers of a key potassium channel in T cells have been shown to be effective treatments for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Our goal is to develop formulations of these peptides that will allow oral administration and thereby enhance their effectiveness as therapeutics.