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.
Prenatal Alcohol Exposure: A Molecular Mechanism For Memory Deficits Involving The Zinc-binding Protein, Metallothionein
Funder
National Health and Medical Research Council
Funding Amount
$277,645.00
Summary
Damage to the developing brain is the major social and economic consequence of prenatal alcohol exposure but it is unclear the mechanism by which this occurs. This study will assess whether the maternal zinc-binding protein, metallothionein, causes: 1) alcohol-related cognitive deficits, 2) changes in the expression of alcohol-sensitive cognitive genes. We will further assess whether dietary zinc supplementation throughout pregnancy can prevent alcohol-related anomalies in neurodevelopment.
Alveolar Macrophage Zinc And Zinc Transporters And Their Role In Phagocytosis
Funder
National Health and Medical Research Council
Funding Amount
$288,975.00
Summary
Zinc is an essential dietary component that serves a number of functions in the lungs. It is both an anti-oxidant and anti-inflammatory agent. Some airway inflammatory diseases such as emphysema may involve a critical loss of lung zinc. We believe that cigarette smoke causes the loss of zinc and this prevents the lung macrophages from working properly to clear bacteria and dead cells. This will provide a foundation for our long term goals of better clinical management of emphysema.
Transgenerational Effects Of Male Obesity - Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$829,143.00
Summary
Childhood obesity is associated with obesity in either parent, and obese children tend to become obese adults, forming an intergenerational cycle that promotes obesity. We have identified paternal obesity as an important novel target for intervention to stop the progression of the obesity epidemic. This project investigates supplementation of obese fathers with folate to prevent the adverse impact of paternal obesity on subsequent generations.
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.
Role Of Zinc In The Respiratory Epithelium And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example ....This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example, asthma affects 12% of adults and amongst these, 15% waken weekly or more often with their asthma while 6% are hospitalized annually. There is a need to understand the basic mechanisms underlying these diseases so that new strategies can be developed to modify bronchocondtriction and inflammation. The project will provide new knowledge concerning the physiology of Zn in the respiratory epithelium and interactions between Zn deficiency and oxidants on injury in the respiratory tract. The usefulness of easily accessible nasal epithelial cells as a measure of Zn and Zn transporter levels deeper in the respiratory tract will be assessed. The project encompasses a number of fields and utilizes in vitro cellular and animal models, as well as tissues from human subjects.Read moreRead less
A Dietary Intervention For Sarcopenia In Cirrhosis
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Patients with chronic liver failure, or cirrhosis, suffer many complications. Sarcopenia, the loss of muscle and muscle weakness, is one of these. It is associated with reduced survival. Patients with cirrhosis have low levels of branched chain amino acids (BCAAs) which are used as building blocks for protein and energy in muscle. We aim to explore how oral supplements of BCAAs might improve muscle in this population. If this improves muscle mass, we also expect it may improve other outcomes.
While is important to prevent vitamin D deficiency, controversies exist about optimal vitamin D intakes and concentrations. Our aim is to evaluate safety concerns with dosages of vitamin D which are routinely promoted for unsupervised public use with over the counter products. We will do this by evaluating long-term health effects for infant vitamin D supplementation, and by using a genetic approach to evaluate the causal effects of high vitamin D and calcium concentrations.
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.
Huntington’s disease is a devastating neurological disorder, with no drugs currently available to cure or treat the underlying cause. Our recent laboratory work on a drug called PBT2 was the foundation of a encouraging clinical trail for this disease. Here, we propose to investigate a drug called Zn(DTSM) for this disease, which has similar properties to PBT2, but we expect will have a greater effect.