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.
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
Understanding Virulence In Staphylococcus Aureus And Impacts On Host Response
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Golden Staph remains an important cause of serious infections in Australian patients. New strategies to combat this disease require a better understanding of how Golden Staph causes disease and escapes the natural human response to infection. This study will provide new insights into how Golden Staph causes disease, and provide a platform for developing new strategies to prevent and treat Golden Staph infections.
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.
Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.
Optimising disease surveillance to support decision-making. COVID-19 has demonstrated the critical role of epidemic data and analytics in guiding government response to pandemic threats, reducing disease and saving lives. The demand for epidemic analytics for response to threats of national significance will only grow. The goals of this project are to 1) determine the combination(s) of surveillance methods that provide the most useful data for epidemic analysis and 2) translate these findings in ....Optimising disease surveillance to support decision-making. COVID-19 has demonstrated the critical role of epidemic data and analytics in guiding government response to pandemic threats, reducing disease and saving lives. The demand for epidemic analytics for response to threats of national significance will only grow. The goals of this project are to 1) determine the combination(s) of surveillance methods that provide the most useful data for epidemic analysis and 2) translate these findings into the blueprint for a next-generation infectious disease surveillance system for Australia. We will use a simulation-evaluation approach, coupling methods from infectious disease modelling with those from information theory optimal design. Outcomes will enable more tailored and effective pandemic response.Read moreRead less
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Multi-Targeted Inhibition Of An Essential Tetrameric Enzyme From Drug -Resistant Streptococcus Pneumonie.
Funder
National Health and Medical Research Council
Funding Amount
$534,313.00
Summary
Streptococcus pneumoniae is an significant human pathogen which causes several diseases including pneumonia and meningitis. Treatment of infection involves the use of antibiotics such as penecillin, however, resistant strains are now emerging. This project will address the real need to develop new antibiotics targeting this organism. This is essentially a drug discovery project which exploits a novel means to target Streptococcus pneumoniae.