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
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.
Structural and functional characterisation of compounds that inhibit the malarial aminopeptidases. Malaria is the world's most prevalent parasitic disease. Due to the rapid spread of drug resistant parasites there is a need to develop new antimalarial drugs. In this proposal we will characterise new targets and novel methods of inhibition that will form the basis of a new mechanism for antimalarial drugs.
Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, thro ....Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, through an examination of mouthpart and gut structure and their types and concentration of digestive enzymes. Information will be used to formulate and test improved diets of appropriate size, texture and nutritional composition and will be the first comprehensive analysis of preferred larval diets on the basis of their biological and physiological characteristics.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.Read moreRead less
Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of ....Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of important membrane proteins are available for these structural studies including ABC transporters, Caveolin-3 and the NS1 protein of Dengue virus, all of which are difficult to crystallize using conventional techniques.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100149
Funder
Australian Research Council
Funding Amount
$590,000.00
Summary
Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit D ....Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit Direct Electron Detection camera system into the established cryo-EM facility managed by the University of Queensland node of the Australian Microscopy and Microanalysis Facility. This will offer unique and significantly improved capabilities for atomic resolution protein structure analysis, and will support a broad range of projects across the biological sciences.Read moreRead less
Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of ....Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of DNA replication in regenerating liver. We shall obtain a detailed picture of the role of this histidine kinase in liver cell biology and an insight into the more general biological role of this class of enzyme.Read moreRead less
A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits wi ....A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits within the complex, or between ATP synthase and other enzyme complex involved in energy production (including other ATP synthase complexes) will be investigated. New and significant insights into one of the most fundamental and challenging enzymes of life will be obtained.Read moreRead less
The Structure Function and Biology of Serpins. The serpin family of proteins control protease activity, in a variety of biological systems, via a dramatic conformational change. We are 4 leaders in the serpin reseacrh field using an integrated approach of biochemistry, biophysics, molecular biology, cell biology, structural biology and bioinformatics to analyse every facet of serpin structure, function and biology. We will apply and develop novel technologies that will determine how these confor ....The Structure Function and Biology of Serpins. The serpin family of proteins control protease activity, in a variety of biological systems, via a dramatic conformational change. We are 4 leaders in the serpin reseacrh field using an integrated approach of biochemistry, biophysics, molecular biology, cell biology, structural biology and bioinformatics to analyse every facet of serpin structure, function and biology. We will apply and develop novel technologies that will determine how these conformational changes are achieved and how they are controlled. Our increased understanding of this inhibitor - enzyme interaction will have implications to other proteins which undergo conformational change and biotechnology.Read moreRead less