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Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100202
Funder
Australian Research Council
Funding Amount
$255,120.00
Summary
Three-dimensional cryo correlative light and electron microscopy facility. This project aims to establish a three-dimensional (3D) cryo-correlative light and electron microscopy facility. The facility will integrate light microscopy with high resolution cryo-electron tomography and 3D slice-and-view focused ion beam scanning electron microscopy. The open access facility should create new capabilities for Australian researchers to tag biological events and structures with fluorescence markers and ....Three-dimensional cryo correlative light and electron microscopy facility. This project aims to establish a three-dimensional (3D) cryo-correlative light and electron microscopy facility. The facility will integrate light microscopy with high resolution cryo-electron tomography and 3D slice-and-view focused ion beam scanning electron microscopy. The open access facility should create new capabilities for Australian researchers to tag biological events and structures with fluorescence markers and image them using the currently highest resolution 3D imaging techniques for biological matter. The facility expects to reveal fundamental insights into cell and structural biology, and help drive innovation in agriculture, pharmaceutics, and biomaterials.Read moreRead less
Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by an ....Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by animals (in venoms and immunity), fungi (in defence) and pathogenic bacteria (in disease). The aim of this project is to image to the highest possible resolution how the MAC form pores in the context of bacterial cells and explore the way it inserts into cells in real time. Intended project outcomes may lay the foundation for applied future research into improved antibiotic delivery and novel pesticide development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100097
Funder
Australian Research Council
Funding Amount
$675,000.00
Summary
An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and c ....An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and crystallisation techniques, including second order nonlinear imaging of chiral crystals (SONICC) imaging and lipid cubic phase approaches, to enable structural studies to be undertaken on challenging proteins. This information is often used for the rational development of therapeutics. The facility would support cutting-edge biological research In Australia.Read moreRead less
How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role ....How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role of these foldases in virulence. The research will reveal how bacterial virulence factors are folded, identify novel targets for therapeutic intervention and provide the basis for structure-based design on new antimicrobials in the future. Read moreRead less
Bio-engineering Insect-Specific Flaviviruses for control of arboviruses. This project aims to study a family of commensal viruses of mosquitoes called insect-specific flaviviruses that are naturally found in mosquitoes and do not infect or cause disease in vertebrate hosts. Using an innovative approach, this project employs cutting-edge molecular virology approaches to modify these insect-specific flaviviruses to enhance their ability to block the replication of other pathogenic viruses in the m ....Bio-engineering Insect-Specific Flaviviruses for control of arboviruses. This project aims to study a family of commensal viruses of mosquitoes called insect-specific flaviviruses that are naturally found in mosquitoes and do not infect or cause disease in vertebrate hosts. Using an innovative approach, this project employs cutting-edge molecular virology approaches to modify these insect-specific flaviviruses to enhance their ability to block the replication of other pathogenic viruses in the mosquito vector. Expected outcome of this project is a bio-control strategy that is complementary to the Wolbachia approach. The anticipated benefits include the advancement of knowledge of insect-specific flaviviruses, and promotion of interdisciplinary research across the fields of Entomology and Virology.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100304
Funder
Australian Research Council
Funding Amount
$416,092.00
Summary
Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of cont ....Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of controlling catalytic activity. The project should significantly increase understanding of several modes of regulation of ubiquitin ligase catalytic activity, and how this controls a myriad of cellular processes. The project will lay the foundation for applied research anti-viral compounds, plant anti-fungals and cancer therapies.Read moreRead less
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.