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.
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.
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.
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.
Uropathogenic Escherichia coli (UPEC) are 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 worldwide. This project addresses the mechanisms by which E. coli ST131 can colonise the urinary tract and cause disease. The outcomes of this project will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regimes for UTI.
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.
Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great pot ....Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.Read moreRead less
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
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less