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.
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
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.
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
Functional Resolution Of PTEX, The Exporter Of Virulence Factors In Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$625,212.00
Summary
Almost half a million people die each year of malaria and nearly half the world’s population are at risk. To eliminate malaria this century we will need new drugs and vaccine to fight the disease. One potential drug target are the molecular gateways called PTEX, that are used by parasites to export virulence proteins into their human host cells. This grant aims to understand how the PTEX molecular machines work so we can develop new drugs to block them and kill the parasites.
Griseofulvin, A Novel Host-directed Antimalarial Drug
Funder
National Health and Medical Research Council
Funding Amount
$461,551.00
Summary
This grant is for a Phase II clinical trial to test an FDA & TGA approved drug for a new use as an antimalarial drug. The parasite uses an enzyme from the human RBC to help it replicate & early trials show this drug appears to disrupt the life cycle of the parasite. This Phase II clinical trial will test the drug on human subjects, & if successful, the drug will be a new and novel way in which to treat and prevent malarial infections in humans.
Malaria In Pregnancy: Exposure, Immunity And Complications
Funder
National Health and Medical Research Council
Funding Amount
$549,723.00
Summary
Increasing malaria control efforts may lead to lack of exposure needed to develop immunity. We will use plasma samples from Africa, PNG and Asia, and measures of immunity we have developed, to discover (1) which are the most important protective immune responses and (2) how are these affected by changing exposure or new drugs. Overall, we hope to identify markers of protective immunity that can be used to identify women at most risk of malaria in pregnancy and its complications
The Structural Resolution Of PTEX, The Translocon Of Virulence Proteins And Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
The extraordinary virulence of malaria parasites is in part due to their ability to export hundreds of proteins into their red blood cell hosts that help them obtain nutrients and avoid the immune system. Recently we discovered the molecular machine that exports proteins into the host cell and we now wish to establish how it works so drugs can be tailored to block the machine and kill the parasites.
The study builds on strong existing NHMRC funded collaborative links between Sri Lanka and Australia in research which has reduced mortality and provided better evidence for treatment of poisoning. Current measurements of kidney damage are slow to change and insensitive. We will study new ways to measure acute kidney toxicity in people with poisoning and snakebite. We aim to determine whether these new measures are better predictors of the short and long term effects on the kidney.
Mechanisms Underlying The Contribution Of Uremic Toxins To Cardiorenal Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$413,533.00
Summary
Cardiorenal syndrome (CRS) is an umbrella term that defines disorders of the heart and kidneys whereby “acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”. We have demonstrated a significant association between heart and kidney fibrosis (scarring) and levels of a uremic toxin called indoxyl sulphate (IS), in relevant animal models and that blockade of production of this toxin reduces cardiac fibrosis. This project aims to explore this association.