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Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integr ....Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integration of Huc, including the basis of its remarkably high affinity and oxygen insensitivity compared to previously studied hydrogenases. This project will enable biotechnological applications, as the first study of an enzyme that extracts energy from air, and has broad ecological and biogeochemical implications.Read moreRead less
How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowled ....How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101173
Funder
Australian Research Council
Funding Amount
$374,318.00
Summary
Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the par ....Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the parasites. Adenylate-forming enzymes play critical roles in a diverse range of biochemical pathways, such as protein translation and fatty acid metabolism. The project seeks to deliver a new paradigm for the design of future antiparasitic agents.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100780
Funder
Australian Research Council
Funding Amount
$455,237.00
Summary
Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecul ....Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecular visualisation technologies, leading to the first molecular description of dynamic processes used by the human replisome. Benefits include improved understanding of a fundamental biological process that often malfunctions in cancers, development of novel methodology, and interdisciplinary training.Read moreRead less
High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. Wit ....High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. With this new technology we aim to identify DNA polymerases with improved performance that benefit biotechnological applications. Additionally, these single-molecule directed-evolution methods will benefit the wider scientific community and lay the foundation for further advances in directed evolution.Read moreRead less
Viral capsids as high-efficiency nanoreactors. This project aims to develop state-of-the-art single-molecule imaging to visualise DNA synthesis inside authentic retroviral capsids in real time. The project expects to generate new knowledge in the fields of virology, synthetic biology, and nanotechnology by utilising cutting-edge fluorescent labelling reagents and microscopy technology. Expected outcomes include a comprehensive description of retrovirus reverse transcription, development of innov ....Viral capsids as high-efficiency nanoreactors. This project aims to develop state-of-the-art single-molecule imaging to visualise DNA synthesis inside authentic retroviral capsids in real time. The project expects to generate new knowledge in the fields of virology, synthetic biology, and nanotechnology by utilising cutting-edge fluorescent labelling reagents and microscopy technology. Expected outcomes include a comprehensive description of retrovirus reverse transcription, development of innovative biophysical techniques for the study of viruses, and an understanding of the engineering principles at play in natural nano-reactors. This project anticipates contributing advanced capabilities in bionanotechnology, benefiting therapeutic, biotechnology and synthetic biology applications.Read moreRead less