Role Of Regulatory Genes In The Gastrointestinal Pathogen, Clostridium Difficile
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
When patients are treated in hospital with antibiotics they sometimes develop chronic diarrhoea or colitis syndromes that are very difficult and expensive to treat. This project involves the analysis of the bacterium that generally causes these gastrointestinal diseases. We know that this microorganism is present in the hospital environment and that it produces potent protein toxins that are responsible for these diseases but we know little about the actual disease process. In most bacteria that ....When patients are treated in hospital with antibiotics they sometimes develop chronic diarrhoea or colitis syndromes that are very difficult and expensive to treat. This project involves the analysis of the bacterium that generally causes these gastrointestinal diseases. We know that this microorganism is present in the hospital environment and that it produces potent protein toxins that are responsible for these diseases but we know little about the actual disease process. In most bacteria that cause disease there are regulatory networks that control the expression of the genes responsible for the disease process. In this project, we aim to develop an understanding of how these regulatory networks operate in this particular bacterium. The latest techniques of molecular biology will be used to investigate several specific regulatory genes at the functional level. Since the entire DNA sequence of this bacterium is now known we will also use a broader research approach that makes use of this knowledge to examine all of potential regulatory networks that exist in this bacterium. Finally, we will develop new methods for the genetic analysis of the causative bacterium so that we will be better able to elucidate the role of specific genes in the disease process. By understanding how this bacterium controls the production of the proteins that interact with human intestinal cells to cause disease we hope to be able to prevent such diseases from occurring. The successful completion of the project therefore will make a major contribution to the development of improved methods for the control and treatment of these chromic diarrhoea and colitis syndromes.Read moreRead less
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.
Virulence Mechanisms In Hypervirulent Epidemic Strains Of Clostridium Difficile.
Funder
National Health and Medical Research Council
Funding Amount
$499,135.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have emerged since 2000, leading to increased incidence and severity of disease in many countries and resulting in epidemics. This project will make a major contribution to our understanding of how these bacteria cause disease and may help to prevent outbreaks of the hypervirulent strains in Australia by identifying potential new vaccine candidates.
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.