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.
DNA sequencing allows us to see into the microbial world in fine detail. This enables us to investigate how bugs like bacteria cause infections and other diseases. In this fellowship, I will use DNA sequencing and analysis to investigate how bacterial infections are transmitted in hospitals and cities, how bacteria become resistant to the antibiotic drugs we use to treat infected people, and how the bacteria that live in our nose and throat contribute to development of asthma in young children.
Determining The Bacterial Contributions To Tuberculosis And Identification Of Drug Targets
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Serious issues of drug resistance have emerged in tuberculosis prevention and are placing enormous pressure on global health systems. We have identified an enzyme of M. tuberculosis that is essential for its survival. This project will develop potent inhibitory compounds for this enzyme. Further, we will identify new drug targets through a screen to specifically identify the genes of the organism essential for its survival in the body. This information will be used to develop new TB drugs.
Structural Characterization Of A Novel AB5 Cytoxin - SubAB
Funder
National Health and Medical Research Council
Funding Amount
$210,760.00
Summary
The proposed research program, using a combinantion of structural biology and biophysical techniques will provide insight into the role of novel AB5 toxin from E. coli. This study will not only improve our fundamental understanding the mode of action of this toxin from this devastating pathogen, but could lead to the design of rational antimicrobials. The knowledge gained will increase Australian international research profile.
Targeting Bacterial ÏsuperbugsÍ By Innovative Combination Dosing Strategies And New Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$463,650.00
Summary
This research project will elucidate the mechanistic basis to optimally combine available beta-lactam antibiotics to prevent resistance of gram-negative bacterial ïsuperbugsÍ. These mechanistic insights will be utilised to develop novel antibiotics that are active against these multidrug-resistant bacteria. The interdisciplinary project will substantially contribute to solving the global crisis due to multidrug-resistant bacteria and inform the design of effective new antibiotics.
Impact Of Pneumococcal Vaccination And Environmental Factors On Pneumococcal Carriage And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$455,872.00
Summary
Pneumonia is the leading killer of children <5y of age worldwide, and the pneumococcal bacterium is a common cause. Pneumococci are carried in the noses of healthy children. In this project we will determine 1) whether carriage can be used to monitor the impact of vaccination in resource-poor settings, 2) the effect of new vaccines on ear disease and transmission using infant mouse models and 3) if exposure to smoke effects the ability of pneumococci to cause disease and altered gene expressi ....Pneumonia is the leading killer of children <5y of age worldwide, and the pneumococcal bacterium is a common cause. Pneumococci are carried in the noses of healthy children. In this project we will determine 1) whether carriage can be used to monitor the impact of vaccination in resource-poor settings, 2) the effect of new vaccines on ear disease and transmission using infant mouse models and 3) if exposure to smoke effects the ability of pneumococci to cause disease and altered gene expression.Read moreRead less
The Hunt For New-generation Lipopeptide Antibiotics Targeting Gram-negative ‘Superbugs’
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
The dry antibiotic discovery and development pipeline, together with the increasing incidence of bacterial resistance in the clinic has been dubbed ‘the perfect storm’. This project involves the design, synthesis and preclinical evaluation of a new generation of polymyxin-like lipopeptides that have low nephrotoxicity and specifically target polymyxin-resistant Gram-negative ‘superbugs’.
Evolutionary Events Shaping The Genome Of Cryptococcus Neoformans And Their Effects On Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Recurring infection in patients with fungal meningitis caused by Cryptococcus neoformans is typically caused by persistence of the original infection rather than reinfection with a new strain. Our analysis of relapse strains shows that small-scale alterations frequently occur at the chromosome ends - regions containing important pathogenesis-related genes in other pathogens. We seek to characterise this microevolution further to understand how it contributes to the success of this pathogen.
Mechanisms Of Disease Caused By Hospital-acquired Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$465,218.00
Summary
We are currently experiencing unprecedented levels of antibiotic resistance in human pathogens. Unfortunately, the drug development pipeline is drying up, with almost no novel therapeutic options expected in the near future. This proposal aims to identify the mechanisms by which the most important antibiotic-resistant human pathogens make us sick. The expected outcomes are the identification of new targets that may be amenable to future drug development. These targets are aimed at making the org ....We are currently experiencing unprecedented levels of antibiotic resistance in human pathogens. Unfortunately, the drug development pipeline is drying up, with almost no novel therapeutic options expected in the near future. This proposal aims to identify the mechanisms by which the most important antibiotic-resistant human pathogens make us sick. The expected outcomes are the identification of new targets that may be amenable to future drug development. These targets are aimed at making the organisms less capable of causing disease in humans.Read moreRead less
Host-pathogen Interaction: The Battle For Supremacy
Funder
National Health and Medical Research Council
Funding Amount
$480,014.00
Summary
This grant will provide salary support for Dr Rowena Bull. Dr Bull's research is focused on understanding the disease process between the human host and the infecting virus. The outcomes of this research will be used to find novel ways to fight viral infections with vaccines and drugs.