A significant proportion of Australian children are at health risk due to environmental metal exposure. It is suspected that exposure to metals during the prenatal period can result in permanent impairment. Human studies are, however, limited by lack of biomarkers that accurately measure exposure at specific times of intrauterine development. We are proposing to develop a novel method that utilizes human primary teeth to provide a direct measure of metal exposure during foetal development.
Novel Perspectives On The Function Of AB5 Toxin B Subunits
Funder
National Health and Medical Research Council
Funding Amount
$1,041,896.00
Summary
AB5 toxins are important virulence factors of pathogenic bacteria. They comprise pentameric B subunits that bind to target cell surfaces and catalytic A subunits that damage host cell functions. This proposal examines a new paradigm wherein the B subunits are significant contributors to cell damage. We will characterize the cytopathic properties of diverse B subunits, particularly those of emerging toxins. This will provide novel insights into pathogenesis and inform development of therapeutics.
Metabolism And Neurotoxicity Of Hemin And Hemin-derived Iron
Funder
National Health and Medical Research Council
Funding Amount
$346,400.00
Summary
Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metaboli ....Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metabolism of hemin by the different types of brain cells. The present project investigates the metabolism and neurotoxicity of hemin in brain cells and will examine the capacity of potential therapeutic agents to protect brain cells from hemin toxicity. The data obtained from this project will advance our understanding of the uptake and metabolism of hemin by the four main types of brain cell, and the factors that are likely to be involved in the neurotoxicity of hemin-derived iron following hemorrhagic stroke. The study will also provide data concerning the relative effectiveness of potential therapeutic agents, and information concerning the cell types, time points and aspects of hemin metabolism that are most effectively targeted by these agents. Such advances will guide the development of therapeutic approaches that are directed at minimising the brain damage which results from hemin-derived iron in humans.Read moreRead less
What Are The Clinical Predictors And Risk Factors For Impaired Child Growth And Development? Following Up The Ha Nam Cohort From Birth To 3 Years
Funder
National Health and Medical Research Council
Funding Amount
$1,189,570.00
Summary
Stunting affects about one third of children under five in developing countries and is a measure of chronic undernutrition. This project will identify pre and postnatal risk factors for impaired child growth and development by monitoring a cohort of infants in Vietnam to three years of age, and developing a predictive algorithm for early detection of those at risk of stunting. Effective preventative measures would improve child health, and prevent a huge burden of disease.
Helicobacter Pylori VacA Toxin: Modulation Of Human Mitochondrial Function By A Bacterial Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
This work will greatly further our understanding of how a bacterium, Helicobacter pylori, causes stomach ulcers and cancer. We will use cutting edge model systems to study the VacA toxin that is secreted from the bacteria and is targeted to human cells. We will examine where the toxin goes and how it affects our cells. It is expected that the improved understanding that will arise from this work will assist researchers to better devise drugs against this prevalent pathogen.
Perinatal Exposure To Household And Environmental Toxins And The Risk Of Asthma And Allergic Disease Up To 25 Years
Funder
National Health and Medical Research Council
Funding Amount
$291,078.00
Summary
Perinatal exposure to household and environmental toxins may increase asthma and allergic disease risk. Adverse exposures in this critical developmental window may have a marked and prolonged effect on health. A birth cohort of high-allergy risk children will be used to investigate the effect of common chemical exposures on the risk of asthma and allergic disease up to 25 years. This evidence could be used to inform guidelines on common household chemical exposures
Snake envenoming is a neglected tropical disease and results in numerous deaths, psychological problems and economic burden. Antivenoms aren't readily available in resource poor countries. The CRE will investigate the effects of venom and antivenom to improve understanding of human envenoming. It will also develop tests for early diagnosis of envenoming and undertake clinical trials of antivenom. These studies will be translated back into clinical practice to improve treatment of snake bites.
To Search For Genetic Causes Of Renal Disease In The Tiwi Island Aboriginal Population
Funder
National Health and Medical Research Council
Funding Amount
$638,721.00
Summary
This project aims to continue work done on identifying the genetic basis to the kidney disease suffered by the Tiwi population from Bathurst and Melville Islands. It is based on the outcomes of the first genome-wide scan in an Aboriginal population. The scan yielded a genetic association to a locus that has led to a very plausible hypothesis. If this hypothesis is correct, and the goal of this project is designed to find this out, then public health measures should be able to halt the progressio ....This project aims to continue work done on identifying the genetic basis to the kidney disease suffered by the Tiwi population from Bathurst and Melville Islands. It is based on the outcomes of the first genome-wide scan in an Aboriginal population. The scan yielded a genetic association to a locus that has led to a very plausible hypothesis. If this hypothesis is correct, and the goal of this project is designed to find this out, then public health measures should be able to halt the progression of this disease in the community.Read moreRead less
Discovery And Development Of Novel Venom Peptide Analgesics
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Professor Lewis will discover and develop new research tools and potential therapeutics from toxins acting on pain pathways. The Fellowship will leverage (i) well-funded collaborations with top Australian and international scientists (ii) the recently established IMB Centre for Pain Research that I lead as inaugural Director, and (iii) an outstanding Institute equipped with leading edge technologies for high throughput and high content discovery and proteomic and transcriptomic analysis.