Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989077
Funder
Australian Research Council
Funding Amount
$225,600.00
Summary
Regional Facility for Real Time Analysis of Molecular Interactions. The ARC Facility for the Analysis of Biomacromolecular Interactions at the University of Wollongong and ANU serves many research groups working at the interface of chemistry and biology with the ultimate aim of drug target identification and drug development. New state-of-the-art instrumentation will enhance their capabilities and enable new activities. Specifically, the new instruments will facilitate characterization of macrom ....Regional Facility for Real Time Analysis of Molecular Interactions. The ARC Facility for the Analysis of Biomacromolecular Interactions at the University of Wollongong and ANU serves many research groups working at the interface of chemistry and biology with the ultimate aim of drug target identification and drug development. New state-of-the-art instrumentation will enhance their capabilities and enable new activities. Specifically, the new instruments will facilitate characterization of macromolecular complexes and enable rapid and precise study in real time of the rates at which molecules interact, under many different experimental conditions. It will strengthen existing collaborations among the partner institutions and provide essential infrastructure for drug development projects.Read moreRead less
Subunit Contacts in a Replicative DNA Polymerase: A New Paradigm for Protein-Protein Interactions? The bacterial DNA polymerase III is a 15-subunit protein that acts as an extraordinary molecular machine to copy both strands of chromosomal DNA at the same time, making DNA at the rate of 1000 base pairs each second without ever falling off the chromosome or making mistakes. This project aims to understand the way its subunits iteract, such that they can form stable complexes that are nevertheless ....Subunit Contacts in a Replicative DNA Polymerase: A New Paradigm for Protein-Protein Interactions? The bacterial DNA polymerase III is a 15-subunit protein that acts as an extraordinary molecular machine to copy both strands of chromosomal DNA at the same time, making DNA at the rate of 1000 base pairs each second without ever falling off the chromosome or making mistakes. This project aims to understand the way its subunits iteract, such that they can form stable complexes that are nevertheless flexible enough to accomplish DNA synthesis. There are applications of this knowledge to discovery of new antibacterial agents and in design of new protein machines.Read moreRead less
The chemical, biochemical, genetic and ecological basis of pollinator-driven speciation in Australian sexually deceptive orchids. The Australian biota offers unique opportunities for illuminating ecological and evolutionary processes of worldwide importance. Focussing on Australian sexually deceptive orchids, this study offers a model system for studies of plant speciation that has already captured the interest of the public, educators and scientists around the world. The project will produce mu ....The chemical, biochemical, genetic and ecological basis of pollinator-driven speciation in Australian sexually deceptive orchids. The Australian biota offers unique opportunities for illuminating ecological and evolutionary processes of worldwide importance. Focussing on Australian sexually deceptive orchids, this study offers a model system for studies of plant speciation that has already captured the interest of the public, educators and scientists around the world. The project will produce multiple graduate students with high quality, cross-disciplinary training. Expertise and tools developed will contribute directly to the conservation of endangered Australian orchids. Thus the knowledge obtained from this research will have immediate practical benefits for the sustainable use of Australia's biodiversity.Read moreRead less
Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissu ....Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissue of Arabidopsis, using both wild-type and previously uncharacterised mutants, and will develop a novel mutational screening strategy to isolate mutants disrupted in plasma membrane or microtubule binding. This research will contribute significantly to a greater understanding of how the plant grows and develops.Read moreRead less
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less
Role of a novel zinc-binding motif in the structure-function of deubiquitinating enzymes. The ubiquitin pathway destroys many proteins that control cell function and growth, by attaching ubiquitin to them and marking them for degradation. Deubiquitinating enzymes (DUBs) regulate protein destruction by controlling the amount of ubiquitin attached. DUBs and the ubiquitin pathway can also be manipulated in biotechnology applications. However, very little is known about the structure/function of DUB ....Role of a novel zinc-binding motif in the structure-function of deubiquitinating enzymes. The ubiquitin pathway destroys many proteins that control cell function and growth, by attaching ubiquitin to them and marking them for degradation. Deubiquitinating enzymes (DUBs) regulate protein destruction by controlling the amount of ubiquitin attached. DUBs and the ubiquitin pathway can also be manipulated in biotechnology applications. However, very little is known about the structure/function of DUBs. We have identified a new zinc-binding motif in DUBs, and we will explore how this contributes to their structure, and interactions with other proteins. This will significantly enhance our knowledge of how DUBs function in both biotechnology and in controlling cell function.Read moreRead less
Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identi ....Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for Plasmodium falciparum infection. Developing novel targets is mandated by humanity, but also to safeguard Australia's region against the social and economic implications of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Enabling Technologies for Structural Genomics. New technologies will be developed to save time, money and effort in rapid preparation of protein samples for structural genomics. Systems will be devised for preparing sufficient isotope-labelled proteins for nuclear magnetic resonance spectroscopy without using living organisms, for efficiently identifying points at which proteins can be broken into smaller fragments with the right properties, and for joining the ends of proteins and peptides toge ....Enabling Technologies for Structural Genomics. New technologies will be developed to save time, money and effort in rapid preparation of protein samples for structural genomics. Systems will be devised for preparing sufficient isotope-labelled proteins for nuclear magnetic resonance spectroscopy without using living organisms, for efficiently identifying points at which proteins can be broken into smaller fragments with the right properties, and for joining the ends of proteins and peptides together to make them much more stable. This combination of technologies are widely applicable to current problems in protein chemistry, molecular biology, functional genomics and the medical sciences.Read moreRead less
3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less