Pathogenomics: New Ways To Exploit Genome Sequence Data From Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$547,372.00
Summary
Bacterial pathogens are locked in an evolutionary battle of survival with their eukaryote hosts. The rapidly evolving genes of medically-important pathogens are generally those required for adaptation to the human host. This project aims to exploit the abundance of available bacterial genome sequences to predict rapid evolution in bacterial pathogens using computational methods. The protein products of such genes offer novel targets for therapeutic intervention.
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.
Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
Contribution Of Nuclear Targeting Of The NleE-OspZ Family Of Proteins To Escherichia Coli And Shigella Virulence
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified new bacterial proteins that allow E. coli to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Shigella which causes dysentary. We will determine how these proteins act by finding the host cell proteins they bind.
Characterisation Of Enterohaemorrhagic Escherichia Coli Lacking Classical Virulence Markers
Funder
National Health and Medical Research Council
Funding Amount
$140,660.00
Summary
Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this ty ....Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this type of E.coli and usually acquire the infection by consuming contaminated food or water. This organism is currently a global food safety problem and the bacteria are especially prevalent in ground beef products and water or vegetables that have been contaminated with cattle faeces. In this study we aim to identify new bacterial genes and proteins that may be used to improve current means of detecting and diagnosing this kind of E.coli. A great deal is known about the way in which the classical strains of this virulent E .coli colonise the intestine however a small but significant group of these organisms do not carry known colonisation factors. We aim to identify bacterial proteins in these non-classical strains of E.coli which are needed for attachment of the bacteria to the host. Identifying how these bacteria interact with the host may help us to develop improved means of detecting and diagnosing this life-threatening infection.Read moreRead less
Development Of Improved Preventative Therapeutic Strategies For The Control Of Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bact ....A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bacterial infections are responsible for >10 million deaths p.a., and the economic impact is inestimable. For most major pathogens, vaccines are either unavailable or have serious shortcomings. Resistance to commonly used antimicrobials is increasing at an alarming rate, and modern travel has assisted the rapid global dissemination of highly resistant and virulent clones. Morbidity and mortality are also predicted to increase as a consequence of human-induced environmental changes and the growing proportion of the population with increased susceptibility to infection. Effective management of bacterial infectious diseases in the 21st century will require a two-pronged approach involving the development of cheaper and more effective vaccines, as well as novel anti-infectives refractory to known resistance mechanisms. However, formulation of optimal therapeutic and preventative strategies demands a thorough understanding of the biology of disease, particularly the complex interactions between bacterial pathogens and their human hosts. I have also played a leadership role in establishing the Pneumococcal Vaccine Consortium, which has just submitted a co-ordinated suite of multicentre proposals to PATH Vaccine Solutions to fund final preclinical testing, GMP scale-up and Phase I-II-III trials of protein-based pneumococcal vaccines that we have developed. The PATH accelerated pneumococcal vaccine development program is of enormous potential significance, because there is now a very real probability of pneumococcal protein vaccines being fast-tracked into human trials. Our aim is to create a direct pipeline from antigen discovery in the collaborators’ laboratories into the clinic. If successful, these vaccines could save millions of lives. This will be of enormous satisfaction to me personally, as it was I who originally proposed and demonstrated “proof of principle” for the vaccine potential of pneumococcal proteins, and I have been advocating assessment of their protective efficacy in humans for over 20 years. Thus, receipt of an Australia Fellowship will undoubtedly further support the internationalisation of Australian medical research.Read moreRead less
Characterisation Of A Novel Type Of Promoter Controlling Expression Of Virulence Genes In Neisseria.
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
This project will investigate how two different types of bacteria control genes that are involved in determining their disease-causing ability. The expression of many bacterial genes is controlled by a sophisticated battery of regulatory systems that respond to individual, very specific, environmental signals. Such regulatory systems are capable of exerting very precise control over the level of gene expression, in response to the concentration of specific molecules in the immediate environment. ....This project will investigate how two different types of bacteria control genes that are involved in determining their disease-causing ability. The expression of many bacterial genes is controlled by a sophisticated battery of regulatory systems that respond to individual, very specific, environmental signals. Such regulatory systems are capable of exerting very precise control over the level of gene expression, in response to the concentration of specific molecules in the immediate environment. However, there is evidence to suggest that many important disease-causing bacteria are much less reliant on specific regulatory systems. Instead, these bacteria rely more heavily what have been termed global systems for the regulation of gene expression. Such systems typically respond to less specific signals, such as the growth rate of the bacterial cell, but nevertheless appear capable of very precise control. We have evidence for a previously uncharacterised type of global control system that appears to be widespread amongst bacteria. It is likely that many virulence genes in a variety of disease-causing bacteria will prove to be controlled by similar means. Therefore this project will not only provide an insight into how expression of these particular virulence determinants is regulated, but will yield data that may help in our understanding of precise global regulatory processes in other bacterial species of medical importance.Read moreRead less
Some bacteria can cause inflammation of the brain (bacterial meningitis). This leads to 170,000 deaths annually in the world. Many patients who survive after antibiotic treatment have lifelong disabilities like deafness, and problems of memory and learning. We aim to show that a certain biochemical pathway in the brain contributes to death and disability, with a view to identifying new drug treatments that can be used alongside antibiotics to improve disease outcomes.