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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
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Biology and evolution of intracellular parasitism. This project will investigate the development of intracellular parasitism in environmental amoebae. The outcomes of this work will help to understand the mechanisms by which bacteria have evolved to survive inside cells and in some cases cause disease.
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.
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.
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.
Nucleomodulin effectors of the environmental pathogen Legionella. This project aims to examine the evolution of Legionella as an intracellular organism and the mechanisms by which the bacteria evade environmental predation by amoebae. Aside from the advancement of knowledge, expected outcomes of this project include a greater understanding of amoebae. This will provide significant benefits, and this knowledge may be used to develop inhibitors of amoebae growth.
Discovery Early Career Researcher Award - Grant ID: DE150100327
Funder
Australian Research Council
Funding Amount
$378,000.00
Summary
Does sex matter? The impact of sex differences on pathogen evolution. Males and females experience the burden of infection differently. Males are typically thought of as the 'sicker sex', favouring investment in costly sexual displays, at the expense of immune function. But what does this mean for the pathogen? Each sex presents a unique set of challenges that an invading organism must overcome; yet the impact of these differences on pathogen evolution has been surprisingly overlooked. This proj ....Does sex matter? The impact of sex differences on pathogen evolution. Males and females experience the burden of infection differently. Males are typically thought of as the 'sicker sex', favouring investment in costly sexual displays, at the expense of immune function. But what does this mean for the pathogen? Each sex presents a unique set of challenges that an invading organism must overcome; yet the impact of these differences on pathogen evolution has been surprisingly overlooked. This project aims to unravel how sex-specific challenges influence the outcome of pathogen evolution. This work will show how infection in males or females can alter the evolutionary potential of disease, and will ask whether same-sex populations could ever lead to the evolution of new pathogen strains and virulence genes.Read moreRead less
Threats of avian pathogens to endangered parrots and human health: developing and utilizing tools for risk reduction. Emerging infectious diseases (EID) are among the most significant threats to conservation, agriculture and public health worldwide. Among these are two globally significant avian pathogens, Chlamydia psittaci and Beak and Feather Disease Virus. This project aims to determine transmission dynamics, fitness costs of infection, and quantify the roles of genetic diversity and host st ....Threats of avian pathogens to endangered parrots and human health: developing and utilizing tools for risk reduction. Emerging infectious diseases (EID) are among the most significant threats to conservation, agriculture and public health worldwide. Among these are two globally significant avian pathogens, Chlamydia psittaci and Beak and Feather Disease Virus. This project aims to determine transmission dynamics, fitness costs of infection, and quantify the roles of genetic diversity and host stress in infection and disease emergence. The project aims to also determine to what extent zoonotic poultry/human infection is related to infection in wild birds. The outcomes aim to be the development of critical knowledge and tools to help manage two avian pathogens causing significant conservation, agricultural and public health concern around the world.Read moreRead less
An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling w ....An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling with a novel experimental protocol to allow the study of kinetics of parasite replication in vivo. Expected outcomes will provide significant benefits, such as new avenues for vaccination and immune intervention.Read moreRead less