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Infectious diseases plague mankind; with infections responsible for approximately 20% of all deaths worldwide. New strategies are urgently needed and we have positioned our research to address questions around how to forestall bacterial pathogens in the initial phases of invasion of human tissues and provide full understanding of the key molecules on the surfaces of bacterial cells. This fundamental knowledge is crucial to new drugs, vaccines and infection-resistant medical devices.
ROLE OF RIP KINASES & IAPs IN MUCOSAL IMMUNE DEFENCE
Funder
National Health and Medical Research Council
Funding Amount
$631,168.00
Summary
Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes in ....Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes infection.Read moreRead less
This program will investigate the strategies used by pathogenic bacteria to cause human diseases. The research will focus on how bacteria initiate infections, how they invade, cause cell and tissue damage and respond to their human host. It will also examine how the host’s innate immune system interacts with these bacteria. The results will provide new insights into host-pathogen interactions and reveal new targets for the development of novel antibacterial drugs and vaccines.
Functional And Genomic Analysis Of The Globally Disseminated Multidrug Resistant Escherichia Coli ST131 Clone
Funder
National Health and Medical Research Council
Funding Amount
$825,537.00
Summary
Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTI) and sepsis. Recently, a highly virulent clone of UPEC (E. coli ST131) that is resistant to multiple types of antibiotics has emerged and spread worldwide. This project uses genomic and high-throughput functional analysis methods to understand E. coli ST131 virulence and resistance. The outcomes of the work will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regim ....Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTI) and sepsis. Recently, a highly virulent clone of UPEC (E. coli ST131) that is resistant to multiple types of antibiotics has emerged and spread worldwide. This project uses genomic and high-throughput functional analysis methods to understand E. coli ST131 virulence and resistance. The outcomes of the work will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regimes for UTI.Read moreRead less
Evolution And Pathogenicity Of NDM-1 Positive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$643,275.00
Summary
Antibiotic resistance (AR), as highlighted by the WHO, is the most pressing medical need of the 21C – some infections are now untreatable. Our research will focus on the new "superbug" NDM-1 positive E. coli. We will correlate AR and pathogenicity and explore the evolution of these "superbugs" using state-of-the-art sequencing. This research will benefit Australian medicine by predicting timelines of AR epidemics and by conducting the first analyses on the virulence potential of these strains.
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
Cryptococcal Meningoencephalitis - Fungal Determinants Of Invasion Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$587,634.00
Summary
Meningitis and brain infection (meningoencephalitis) due to the fungus Cryptococcus, affect over 1 million patients with AIDS annually, especially in developing countries; with more than 600,000 deaths. It is not known how Cryptococci cross from the blood stream into the brain; this must be elucidated in order to prevent and/or control this devastating infection. This project will determine how cryptococci influence host blood cells to act as “Trojan horses” and/or release products that initiate ....Meningitis and brain infection (meningoencephalitis) due to the fungus Cryptococcus, affect over 1 million patients with AIDS annually, especially in developing countries; with more than 600,000 deaths. It is not known how Cryptococci cross from the blood stream into the brain; this must be elucidated in order to prevent and/or control this devastating infection. This project will determine how cryptococci influence host blood cells to act as “Trojan horses” and/or release products that initiate invasion of brain tissue and meningitis.Read moreRead less
Signalling Pathways And Fungal Virulence – The Inositol Polyphosphate Kinase Pathway In Cryptococcus Neoformans
Funder
National Health and Medical Research Council
Funding Amount
$545,189.00
Summary
Bloodstream fungal infections kill millions of people per year world-wide and are costly to treat. A potentially fruitful strategy for developing new, urgently-needed drugs to fight these infections, is to target signalling pathways, which in fungi, are essential for establishing infection. This proposal investigates how one such pathway, the inositolpolyphosphate kinase pathway, allows fungi to establish infection and will determine which components are suitable targets for drug development.
Identifying Key Players In The Spread Of Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$817,448.00
Summary
Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australi ....Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australia.Read moreRead less
Bacterial Pathogenomics: Whole-genome Sequencing To Investigate Infection Transmission, Pathogenesis And Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$475,946.00
Summary
As bacterial superbugs – resistant to multiple antibiotics – dominate the headlines, the pipeline for new antibiotics has all but dried up. High-throughput DNA sequencing heralds a golden opportunity for infectious disease research. By studying the entire collection of genes - the genome - of large numbers of multidrug resistant bacterial strains, we aim to better understand the genetic changes that govern the emergence and global spread of superbugs and translate these findings into the clinic.