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
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.
The Bioactivity And Binding Partners Of Irukandji And Box Jellyfish Venom
Funder
National Health and Medical Research Council
Funding Amount
$596,950.00
Summary
Venom from the Box Jellyfish and Irukandji jellyfish are considered the most leathal known to science yet precious little is known on the nature of these secretions or how they harm humans. This study aims to fully characterise bioactive proteins in jellyfish venom and attempt to block their activity using regulatory-approved and experimental drugs.
Understanding How Toxins Interact With Lipid Membranes And Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$598,220.00
Summary
Chronic pain affects one in five Australians and current treatments have limited effectiveness, with only about one third of patients getting meaningful, pain relief. The aim of the current project is to create alternative treatments for pain that can potentially lead to the reduced suffering and improvement of life quality of many Australians. To achieve this aim we propose to study how spider toxins interact with cells and deactivate sensor targets responsible for chronic pain.
Harnessing The Type VI Secretion System ‘combat’ Arsenal Of A. Baumannii As A Source Of New Antimicrobials And Antimicrobial Targets
Funder
National Health and Medical Research Council
Funding Amount
$521,557.00
Summary
Infections caused by drug-resistant bacteria represent one of the greatest threats to human health. There is an urgent need to develop novel drugs and treatment strategies to combat infections by these drug-resistant organisms. We have shown that the bacteria A. baumannii uses a needle-like system to deliver lethal toxins into competitors. We will characterize these toxins so that we can manipulate them as weapons for controlling infections with multi-drug resistant bacteria.
The Impact Of Clostridium Difficile Infection And The Host Immune Response On Colonic Homeostasis And Regeneration.
Funder
National Health and Medical Research Council
Funding Amount
$932,212.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.