Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
Regulatory Networks Controlling Virulence In Neisseria Gonorrhoeae And Neisseria Meningitidis.
Funder
National Health and Medical Research Council
Funding Amount
$147,500.00
Summary
Bacteria that cause disease produce substances called virulence determinants, often on their cell surface. These virulence determinants are either directly involved in allowing infection to take place, or cause the damage that we recognize as an infectious disease. Some virulence determinants are produced all the time, while others are only made under particular conditions, that is, their expression is regulated. To target efforts in the development of new vaccines and treatments, it is importan ....Bacteria that cause disease produce substances called virulence determinants, often on their cell surface. These virulence determinants are either directly involved in allowing infection to take place, or cause the damage that we recognize as an infectious disease. Some virulence determinants are produced all the time, while others are only made under particular conditions, that is, their expression is regulated. To target efforts in the development of new vaccines and treatments, it is important to identify all the virulence determinants produced by a particular bacterial species, but also to know which are regulated, and the environmental signals that determine their expression. Neisseria gonorrhoeae and Neisseria meningitidis are two important disease-causing bacteria that exclusively infect humans and cause gonorrhoea, and meningitis. The complete DNA sequence of both of these bacteria is now known. From computer analysis of these data, it appears that these bacteria have few of the specific regulatory systems that are present in other bacteria. Because of the limited repertoire of regulatory systems still present in N. gonorrhoeae and N. meningitidis, it is feasible to mutate each one and determine which are involved in regulation of virulence determinants. We have made copies of every individual gene found in the DNA sequence of these bacteria and have attached each one individually to a glass slide to form a microarray measuring 18mm x 18mm. This microarray will allow us to monitor the expression of every gene in these bacteria in response to environmental signals. This information will be used to identify all the virulence genes controlled by each regulatory system. Such an analysis has never been previously achieved for any bacterial species, because of the number and complexity of the regulatory systems usually present.Read moreRead less
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