Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
Defining The Role Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$870,925.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $1 billion annually. This proposal aims to define the role of the transition metal zinc in innate immune resistance to bacterial infection. This knowledge will reveal new targets for next generation antimicrobial therapeutics.
The Role Of Metals In Healthy Brain Aging: Identification Of Novel Compounds To Prevent Age-related Cognitive Decline
Funder
National Health and Medical Research Council
Funding Amount
$789,733.00
Summary
This grant will explore the basic mechanisms that underlie normal learning and memory. Specifically, we are focussing on how the modulation of metal levels may occur with age, and how this may cause or at least contribute to age-related cognitive impairment. We are also examining a novel therapeutic compound for the treatment of cognitive dysfunction. This work will have implications for both normal and pathological ageing.
Defining The Role Of Zinc In Human Macrophage Responses To Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$592,049.00
Summary
It is estimated that one third of the worlds population is affected by mild to moderate zinc deficiency, and that this predisposes to a range of infectious diseases. The immunomodulatory effects of zinc have been appreciated for many years, and indeed zinc supplementation is used to treat severe diarrhoeal diseases. This project aims to understand the anti-infective mechanisms of zinc by focusing on macrophages, a key cell type involved in killing invading microorganisms.
Zinc As An Antimicrobial Agent And Its Effect On The Pathogenesis Of Group A Streptococcus
Funder
National Health and Medical Research Council
Funding Amount
$352,359.00
Summary
This proposal focuses on Group A Streptococcus (GAS), a human pathogen estimated to cause 600,000 human deaths per year. We have shown that the host immune system uses zinc as an antibacterial agent and that GAS has processes that protect against zinc overload. We will determine the way in which zinc mobilization controls GAS infection and how GAS responds to to an increase in zinc concentration. The results will provide new insights into zinc’s role in protection against bacterial infections.
Metal-mediated Mechanisms And Therapeutic Approaches For Treating Brain Injury Across Age
Funder
National Health and Medical Research Council
Funding Amount
$1,229,769.00
Summary
This grant will examine the role of zinc and iron in the neuronal changes that occur following brain injury, with a specific focus on the role of these metals in functional outcomes. We will also examine how the role of these metals changes across the normal lifespan, and also whether these metal changes are consistent across different types of brain injury. Finally, we will examine the therapeutic potential of zinc- and iron-targeted compounds.
Exploiting Increased Autophagy In Bronchial Epithelial Cells: A New Therapeutic Approach For Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$724,161.00
Summary
COPD is incurable, a leading cause of death, and new therapies are urgently needed. Autophagy is a cell response to cell stress conditions, however increased autophagy is harmful. We will investigate the association of increased autophagy with COPD and smoking and evaluate therapies that can reduce autophagy, including zinc-related drugs and novel antibiotics that have been modified to lose their anti-bacterial activity.
Designer DNA-binding Proteins Targeting Methylated DNA For Research And Therapeutic Purposes
Funder
National Health and Medical Research Council
Funding Amount
$583,444.00
Summary
A number of human genes function to suppress the onset or progression of cancer. In cancer sufferers, these genes are often switched off. The aim of this project is to engineer designer protein molecules that will be able to switch these tumor suppressor genes on again in a selective manner. Because the switching off of tumor suppressor genes is common to all forms of cancer, the new technology created in this work will potentially benefit patients suffering from any of a wide range of cancers.
The Role Of PARK9 And Autophagy In Parkinson's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$396,198.00
Summary
With an ageing population, the health burdens of neurodegenerative diseases such as Parkinson's disease (PD) are numerous. We have found a role for a PD suspectibility gene, PARK9, in autophagy- a neuroprotective degradative pathway, that may also be involved in keeping ÎSyn, a pivitol protein in PD, levels in check.