Identifying The Site/s Of Modification On The Human L-type Ca2+ Channel Protein Isoforms During Oxidative Stress With Reference To Development Of A Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$360,369.00
Summary
A rise in calcium and free radicals in the heart are associated with the development of heart disease. We have good evidence that a protein in the heart muscle known as the L-type calcium channel mediates changes in calcium in response to free radicals. This proposal will identify how the channel function is altered by free radicals so that a therapeutic target can be designed to prevent altered channel function and development of heart disease during increases in free radicals.
Reduction Of Oxygen After Cardiac Arrest: The EXACT Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,891,021.00
Summary
We aim to conduct a Phase 3 multi-centre, randomised, controlled trial to determine whether reducing oxygen administration to target a normal level as soon as possible following successful resuscitation from out-of-hospital cardiac arrest, compared to current practice of maintaining 100% oxygen, improves patient survival at hospital discharge.
The Structural Basis For Promiscuity Of Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$713,035.00
Summary
Special proteins called ion channels control the electrical activity of the heart. Drugs that block ion channels can have the unwanted side-effect of altering the rhythm of the heart beat and causing sudden cardiac death. Extensive efforts are made to screen for this problem during drug development but it is still an inexact science. Here we will use high resolution imaging technologies to get a better understanding of how drugs bind to ion channel proteins.
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
Do Exposures Before Conception Influence The Risk Of Asthma In Offspring?
Funder
National Health and Medical Research Council
Funding Amount
$688,586.00
Summary
Asthma and poor lung function are major causes of public health issues. Emerging evidence suggests adverse exposures even before the conception of a child may cause these conditions. The proposed project is part of an international study across generations to identify these factors. This study will provide novel evidence to guide interventions and identify studies to advance this area further. These original findings will be of great importance both nationally and internationally.
Clinical Trial Of A Suprachoroidal Visual Prosthesis For The Profoundly Vision Impaired
Funder
National Health and Medical Research Council
Funding Amount
$1,098,802.00
Summary
For 15 years we have been designing a bionic eye. We have made a device called the Phoenix99 and shown in short term animal tests that it is both safe to implant but also that it potentially performs better than any other device in the world. We are requesting funds to complete longer term animal testing of the device and then commence a small human clinical trial to demonstrate the benefits of the technology – specifically that it is able to help blind people navigate without assistance.
Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
Autoimmune-based thrombocytopenia can be a life-threatening adverse event associated with viral load, surgery, drug therapies or the use of the anticoagulant, heparin. This grant will define mechanisms of anti-platelet antibody-dependent platelet activation and assess shedding of platelet-specific glycoprotein (GP)VI as an immediate consequence of this activation, provide a new strategy for evaluating risk of thrombosis in HIT.
The Role Of Duffy And PF4 In The Platelet Killing Of Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$350,045.00
Summary
Platelets in the blood can kill the Plasmodium parasite, which lives inside red blood cells and causes malaria. Platelets bind parasite-infected red cells and release a molecule that is toxic to the parasite. This project will study why a red cell molecule called Duffy is also needed for this function of platelets. Most Africans carry a gene for Duffy that stops its expression in red cells, and may therefore be more susceptible to malaria because their platelets cannot kill the malaria parasite.