The Molecular Basis Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$16,230,996.00
Summary
Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as ....Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as novel drugs. These are urgently needed to reduce death and illness due to bacterial infectious diseases in the 21st century. 11Read moreRead less
Ecto-nucleoside Triphosphate Diphosphohydrolases Of Leishmania: Role In Virulence And Potential As Antimicrobial Targets
Funder
National Health and Medical Research Council
Funding Amount
$314,658.00
Summary
Leishmaniasis is a serious disease that affects millions of people worldwide, particularly in developing countries. The disease is caused by a number of species of parasites, and current treatment regimes are not ideal. This research aims to target certain proteins produced by the parasite and define the role of the proteins in causing disease. Furthermore this research will identify new drugs that will block these parasite proteins and may contribute to new therapies for this serious disease.
Host-pathogen Interactions In Burkholderia Infection
Funder
National Health and Medical Research Council
Funding Amount
$490,322.00
Summary
Melioidosis is a fatal tropical disease caused by a bacterium Burkholderia pseudomallei. We found that when the bacterium infects macrophage-like cells in culture (that normally kills bacteria), the cells turn into a cell like an osteoclast, a cell that normally degrades bone. Since an osteoclast is unable to kill bacteria, we speculate that the bacterium subverts the macrophage differentiation pathway and directs the cells into a state where it is unable to attack the invading bacteria.
The Molecular Physiology Of Streptococcus Pneumoniae During Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$232,504.00
Summary
The project will determine the way in which pneumococcus changes its properties when it invades the bloodstream of the human host. Since these changes are linked to sepsis then this new understanding will provide information that can be used to manage and control acute pneumococcal infection.
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder. The work has implications for the development of new approaches to prevent and treat UTI.
Copper And Its Antibacterial Action: An Emerging Aspect Of Host Defence Against Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$454,858.00
Summary
This project will determine the way in which copper is used as an antimicrobial agent to kill Salmonella that reside inside the macrophage (white blood cell) of the host and also determine how Salmonella defends against copper-dependent killing. It will also determine the role of copper in the killing of extra-intestinal pathogens during sepsis. These results will provide information that can be used to manage and control infections intracellular and extracellular bacterial pathogens.
Targeting The Mannose Activation Pathway In Leishmania - Novel Drug Targets And Vaccines.
Funder
National Health and Medical Research Council
Funding Amount
$338,661.00
Summary
Leishmaniasis is a parasitic disease ranging in severity from skin lesions to fatal systemic infection. It is a serious public health problem throughout many regions of the world. Co-infection with HIV has emerged as a serious problem in Africa, South America and southern Europe. Recently, leishmaniasis has been identified in East Timor and in kangaroos in Australia. Treatment of leishmaniasis is based on chemotherapy, but currently used drugs are expensive, have high toxicity and unwanted side ....Leishmaniasis is a parasitic disease ranging in severity from skin lesions to fatal systemic infection. It is a serious public health problem throughout many regions of the world. Co-infection with HIV has emerged as a serious problem in Africa, South America and southern Europe. Recently, leishmaniasis has been identified in East Timor and in kangaroos in Australia. Treatment of leishmaniasis is based on chemotherapy, but currently used drugs are expensive, have high toxicity and unwanted side effects. They have also been compromised by the emergence of resistance in the parasite. Leishmania synthesises a range of surface molecules, which are needed for virulence and parasite survival in the host. The biosynthesis process of these molecules requires activated mannose. We have identified two novel parasite genes encoding for enzymes, which are essential for the biosynthesis of surface virulence factors. When either of these genes is deleted the parasite can no longer cause disease. This suggests that drugs targeting the two enzymes will be able to control the infection. We will produce crystals of these enzymes and solve their 3D structure using state of the art technology to screen libraries of synthetic chemicals to find candidate inhibitors of enzyme activity. When these compounds are identified we will use computer modelling to design compounds based on these inhibitors and crystal structure, which will lead to a new generation of anti-Leishmania drugs. We will also determine whether the avirulent parasites can be used as an attenuated vaccine. Recovery from infection leads to a solid immunity and protection from subsequent infection indicating that vaccination is feasible, but despite of a huge amount of research there is no antileishmanial vaccine currently available. This study will lead to potential novel antileishmanial drugs and vaccines. It will also provide fundametal new knowledge of the structure of enzymes critical for parasite virulence.Read moreRead less
Characterisation Of Extracellular DNases Of Pseudomonas Aeruginosa And Their Contribution To Disease
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterium Pseudomonas aeruginosa causes a number of serious diseases of humans particularly of immunocompromised patients. We have found that this bacterium secretes enzymes that have the ability to digest DNA. This proposal aims to work out how this bacterium uses these enzymes to infect human tissues and escape killing by immune cells. The results from this study will help to determine if these proteins may be used as targets for the development of new anti-infective drugs.
Molecular Basis Of Asymptomatic Colonization Of The Human Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$461,894.00
Summary
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder and the surface of urinary catheters. The work has implications for the development of new approaches to prevent and treat UTI ....Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder and the surface of urinary catheters. The work has implications for the development of new approaches to prevent and treat UTI.Read moreRead less