Global Regulation Of Toxin Production In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$389,860.00
Summary
This project involves an investigation of how the bacteria that cause an often fatal wound infection control the production of the toxic proteins that are essential elements of the disease process. In all pathogenic bacteria there are specific genes that encode the virulence factors that are involved in the disease. The expression of these genes is generally controlled by the products of other genes known as regulatory genes. The function of these regulatory networks is generally responsive to e ....This project involves an investigation of how the bacteria that cause an often fatal wound infection control the production of the toxic proteins that are essential elements of the disease process. In all pathogenic bacteria there are specific genes that encode the virulence factors that are involved in the disease. The expression of these genes is generally controlled by the products of other genes known as regulatory genes. The function of these regulatory networks is generally responsive to environmental stimuli. This project involves the detailed functional analysis of a regulatory network that was first identified in this laboratory and which controls the expression of extracellular toxins that have been implicated in gas gangrene. The overall objectives of the project are to develop a detailed understanding of the mechanisms involved in this regulatory process. Specifically, the project aims to determine the functional components of the regulatory proteins that interact with the environmental signal or which bind to the genes encoding the bacterial toxins, to determine the nature of the target sites to which the regulatory proteins bind, and to examine the hypothesis that there is another regulatory gene that is involved in this process. The project will make a major contribution to our knowledge of the complex interactions that occur between an invading bacterium and the host tissues. If we are to fully comprehend how bacteria cause disease then it is critical that we understand how bacteria control the production of the toxic products that are an integral part of the disease process.Read moreRead less
Understanding The Biosynthesis Of Complex Polyketide Lipid Toxins In Pathogenic Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$298,898.00
Summary
Some major infectious diseases such as tuberculosis are caused by bacteria that make very unusual lipids (fats) that can kill human cells or interfere with the human immune system. The aim of this project is to work out how bacteria make these lipids. This knowledge will open up new avenues for treatments to stop bacterial lipid production and prevent disease. There are also potential applications in harnessing the bacterial lipid machinery to make new drugs and a wide range of other chemicals.
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.
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
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.
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.