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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100177
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Advanced electron paramagnetic resonance (EPR) facilities for chemical, biological and materials sciences. New instrumentation to advance national research in hydrogen fuel generation from renewable sources, new generation photo-voltaic technologies, novel polymer and other chemical materials and advanced computing systems will be provided by this project. A new high sensitivity electron paramagnetic resonance facility, located at the Australian National University, will serve researchers in the ....Advanced electron paramagnetic resonance (EPR) facilities for chemical, biological and materials sciences. New instrumentation to advance national research in hydrogen fuel generation from renewable sources, new generation photo-voltaic technologies, novel polymer and other chemical materials and advanced computing systems will be provided by this project. A new high sensitivity electron paramagnetic resonance facility, located at the Australian National University, will serve researchers in the ACT region devoted to the broad range of activities summarised above. A particular focus involves novel, biologically inspired energy systems and high efficiency solar cell technology.Read moreRead less
Allosteric regulation, molecular structure and function of transglutaminase 2. With Australia's ageing population, we can expect to see increasing prevalence of pathologies such as cancer, Alzheimer's disease, and cataracts. The ubiquitous enzyme transglutaminase 2 (TG2) has been implicated in all of these age-related diseases, as well as in chronic disorders such as coeliac disease and diabetes, and may contribute in a positive way to wound healing. Understanding how TG2 is activated and inac ....Allosteric regulation, molecular structure and function of transglutaminase 2. With Australia's ageing population, we can expect to see increasing prevalence of pathologies such as cancer, Alzheimer's disease, and cataracts. The ubiquitous enzyme transglutaminase 2 (TG2) has been implicated in all of these age-related diseases, as well as in chronic disorders such as coeliac disease and diabetes, and may contribute in a positive way to wound healing. Understanding how TG2 is activated and inactivated, and how it selects its targets, will be a critical addition to current knowledge of this enzyme, and will be an essential prerequisite for the development of TG2-targetted drugs and other TG2-related therapies.Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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Inhibitors Of Hypoxanthine-guanine-xanthine Phosphoribosyltransferase As Versatile Drugs To Treat Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$766,163.00
Summary
Due to the increase in resistance to many of the frontline drugs to treat bacterial and parasitic infections, there is an urgent need to develop new pipelines for drug discovery against the pathogens that are causative agents of this diseases. This project pioneers the blocking of nucleotide synthesis to develop new drug leads to treat malaria, human tuberculosis, African sleeping sickness, Chagas disease and uropathogenic E.coli infections.
Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium conce ....Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium concentration, phosphorylation and membrane composition, and isolate its charge-transporting steps. The results will have immediate impact on the understanding of the enzyme's mechanism, its metabolic control and its role in disease.Read moreRead less
Inhibitors Of Biotin Protein Ligase: A New Class Of Antibiotic Targetting Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
The rise of drug-resistant "superbugs" is a major healthcare concern in hospitals around the world. New antibiotics are needed to combat infections caused by bacteria that are resistant to current drugs. One collaborative team of researchers is addressing this issue. They have discovered a new drug effective against Staphylococcus aureus, the cause of Golden Staph using a combination of scientific disciplines the team is now moving forward and improving their exciting new drug.
The Biosynthesis Of Mycobactin T, A Virulence Factor From Mycobacterium Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Mycobacterium tuberculosis is the causative agent of tuberculosis. The drug isoniazid led to a dramatic and sustained decline in mortality due to tuberculosis. This led to it being described in medical literature in 1988 as a disappearing disease which was now fairly easy to treat. However, the advent of HIV and the rapid rise of multidrug resistant M. tuberculosis led to dramatic changes. The risk that an HIV infected individual will develop active tuberculosis is 7% per year, compared to a lif ....Mycobacterium tuberculosis is the causative agent of tuberculosis. The drug isoniazid led to a dramatic and sustained decline in mortality due to tuberculosis. This led to it being described in medical literature in 1988 as a disappearing disease which was now fairly easy to treat. However, the advent of HIV and the rapid rise of multidrug resistant M. tuberculosis led to dramatic changes. The risk that an HIV infected individual will develop active tuberculosis is 7% per year, compared to a lifetime risk of 10% for an immunocompetent person. Similarly, the prevalence of drug resistant strains of M. tuberculosis is over 5% in many regions, including SE asia. Mycobacterial infections are regarded as the leading cause of morbidity and mortality world wide and WHO estimates that 30 million deaths will occur in the next decade due to these infections. Clearly, new drugs are required to combat the rising menace of this organism. The aim of this project is to detail the unique metabolic pathways in M. tuberculosis that produce Mycobactin T, essential to the virulence of this organism. Mycobactin T helps the bacteria obtain iron, an essential nutrient. These factors make the mycobaction pathway an ideal drug target and an understanding of its biochemistry is essential to its eventual exploitation for intervention in M. tuberculosis infections. We hypothesise that it may already provide the unknown site of action of a clinically employed, antituberculosis drug para-aminosalicylate (PAS). This project will i) fully define the structure of mycobactin T; ii) clone and overexpress key genes which catalyse the first three steps of mycobactin formation; iii) purify and characterise the overexpressed proteins with respect to their biochemical function; iv) examine the interaction of PAS with the proteins likely to be targeted by this antimycobacterial agent. The results of this work will provide the basis for the development of future anti-tuberculosis drugs.Read moreRead less
Characterising and exploiting hydrogen tunnelling in environmentally and medically important enzymes. Theory and experiment will be used to study environmentally and medically important enzymes, and quantify the role that hydrogen tunnelling plays in their activity. The project will determine the basis of their remarkable ability to catalyse chemical reactions, and to engineer and design more efficient proteins and pharmaceuticals.
Flaviviral Proteases As Viable Targets For Antiinfective Drugs
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Viruses hijack the machinery and nutrients of cells they infect in order to reproduce. We will study viral enzymes (proteases) essential for virus replication, use fluorescent probes to learn where the viral enzymes hide and act in infected cells, track the passage of drugs aimed at these enzymes, design drugs to block their actions and stop virus replication, and test antiviral activity against Dengue, West Nile, Japanese Encephalitis and Yellow Fever viruses which infect millions of people.