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Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, ....Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, for example in disease such as diabetes or transplant rejection. Furthermore, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the ....Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the host's immune system will also be gained. The techniques established during the study of MSP-2 will be useful for the study of larger proteins and protein complexes from many systems in the future.Read moreRead less
Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nan ....Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nanotechnology would therefore benefit from this work by basing their designs on the principles behind the mechanism of the bacterial motor. This research is also of interest for veterinary science, as motility by flagellar motor is a key virulence factor of common animal pathogens associated with, for example, listeriosis and gastroenteritis.Read moreRead less
Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasit ....Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasite-infected red blood cells. We will examine the roles of oxidative stress and of parasite proteins in modulating the properties of the host cell membrane.Read moreRead less
Transporting proteins to and within mitochondria. Mitochondria are found in all of our cells and are essential for life. They act like a nuclear power plant, providing the bulk of energy - but they can also kill the cell if the mitochondrial wall (membrane) is opened. Mitochondria contain about 1000 different proteins to function properly but almost all of them are made outside the compartment and must squeeze in through narrow membrane channels. This project will provide new insights into how p ....Transporting proteins to and within mitochondria. Mitochondria are found in all of our cells and are essential for life. They act like a nuclear power plant, providing the bulk of energy - but they can also kill the cell if the mitochondrial wall (membrane) is opened. Mitochondria contain about 1000 different proteins to function properly but almost all of them are made outside the compartment and must squeeze in through narrow membrane channels. This project will provide new insights into how proteins get into mitochondria and what factors help in this process. Besides providing new information about a process that is essential for life, the project will train students in molecular cellular biology techniques and will help foster strong international collaborations.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775708
Funder
Australian Research Council
Funding Amount
$289,680.00
Summary
X-ray Diffraction Microscope. The results of the research will substantially expand Australia's knowledge base in the area of diffraction, imaging and structural biology. It will build up our expertise in x-ray optics and synchrotron technology, and will open up a new approach to x-ray imaging and structure determination.
This will revolutionize our understanding of cellular and sub-cellular organisation with implications for the treatment of disease while the ability to determine structures ....X-ray Diffraction Microscope. The results of the research will substantially expand Australia's knowledge base in the area of diffraction, imaging and structural biology. It will build up our expertise in x-ray optics and synchrotron technology, and will open up a new approach to x-ray imaging and structure determination.
This will revolutionize our understanding of cellular and sub-cellular organisation with implications for the treatment of disease while the ability to determine structures of membrane proteins will open the door to fresh opportunities in rational drug design and biotechnology that will promote innovation in this industry, and the likely foundation of new start-up companies.Read moreRead less
The functional organisation of the trans-Golgi network: From cultured cells to physiological systems. This research will result in a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will impact on cell biology in the broadest sense, from membrane biogenesis to lipid domain organization, as well as membrane transport, protein structure and protein targeting. Furthermore, this work will utilize and develop fronti ....The functional organisation of the trans-Golgi network: From cultured cells to physiological systems. This research will result in a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will impact on cell biology in the broadest sense, from membrane biogenesis to lipid domain organization, as well as membrane transport, protein structure and protein targeting. Furthermore, this work will utilize and develop frontier technologies of live cell imaging and RNA interference as a genetic tool to investigate functions of a protein family. By training post-graduate students and post-doctoral staff, it will contribute to the expertise of cell biology in Australia. International collaborations will enhance connections between Australia and overseas research.Read moreRead less
Searching for novel protein domains: A bioinformatic analysis of whole proteomes. The functional annotation of the set of proteins encoded by a whole genome (the "proteome") is a crucial component of genome research. The aim of this project is to extend the functional and structural annotation of large protein databases by identifying novel protein domain families and building a novel domain library. Our approach is semi-automated and fast, thanks to execution in the fastest parallel supercom ....Searching for novel protein domains: A bioinformatic analysis of whole proteomes. The functional annotation of the set of proteins encoded by a whole genome (the "proteome") is a crucial component of genome research. The aim of this project is to extend the functional and structural annotation of large protein databases by identifying novel protein domain families and building a novel domain library. Our approach is semi-automated and fast, thanks to execution in the fastest parallel supercomputer in Australia available at the Victorian Partnership for Advanced Computing. Our preliminary data demonstrates that our method is feasible.Read moreRead less
Autophagy and the nucleus. Autophagy is a degradation pathway that is essential for survival, internal change (differentiation and development) and maintenance of physiological equilibrium (homeostasis). Moreover autophagy serves to protect higher organisms against infections, cancer and neurodegeneration. This project seeks to better understand the mechanisim by which parts of the nucleus can be degraded by autophagy and how this relates to diseases which may involve defects in, or abnormal deg ....Autophagy and the nucleus. Autophagy is a degradation pathway that is essential for survival, internal change (differentiation and development) and maintenance of physiological equilibrium (homeostasis). Moreover autophagy serves to protect higher organisms against infections, cancer and neurodegeneration. This project seeks to better understand the mechanisim by which parts of the nucleus can be degraded by autophagy and how this relates to diseases which may involve defects in, or abnormal degradation of nuclear components. Benefit will accrue from a contribution to knowledge with future potential to impact on disease, as well as strengthening links with the international network working in the field of autophagy.Read moreRead less