Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.Read moreRead less
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882512
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefit ....Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application aims to enhance existing genomic technologies by adding platforms that will increase the scope of experiments that can be performed as well as providing automation and increased capacity to handle the increasing demand for these techniquesRead moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989147
Funder
Australian Research Council
Funding Amount
$950,000.00
Summary
Advanced high throughput genomics facility for biological, medical, agricultural, environmental and evolutionary research. Infrastructure requested will expand the capacity of researchers in NSW/NT to undertake environmental, medical and evolutionary studies using state-of-the-art technologies based on the recent advances in DNA sequencing analyses. It will ensure the retention of leading researchers in the exciting areas of genomics and Systems Biology and make a significant contribution to bi ....Advanced high throughput genomics facility for biological, medical, agricultural, environmental and evolutionary research. Infrastructure requested will expand the capacity of researchers in NSW/NT to undertake environmental, medical and evolutionary studies using state-of-the-art technologies based on the recent advances in DNA sequencing analyses. It will ensure the retention of leading researchers in the exciting areas of genomics and Systems Biology and make a significant contribution to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application will enhance existing genomic technologies by substantially increasing the scope of experiments that can be performed leading to important advances in gene discovery.Read moreRead less
The structure and function of dihydroorotase - an enzyme essential for pyrimidine biosynthesis. Malaria has recently re-emerged as one of the major life threatening diseases worldwide. With increasing travel and climate change, malaria is increasingly endangering Australians at home and abroad. Our work aims to provide the basis for the rational design of a new class of anti-malarial drugs by the systematic and thorough analysis of an essential enzyme in the malarial parasite.
Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in orga ....Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in organic solvents, especially chiral resolution of mixtures in the production of pharmaceutical intermediates. Genetic improvement of lipase enantiospecificity and regioselectivity will be achieved using in vitro evolution by recombination and screening. The outcome will be cost-effective production superior biocatalysts with specifically enhanced regiospecific, enantioselective and hydrolytic characteristics.
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Structural elucidation and functional analysis of insulin-like growth factor binding protein-3 domains. Translating information from the human genome project into information about cell function is a major challenge in the post-genome era. The multifunctional insulin-like growth factor binding protein-3 (IGFBP-3), a member of a multigene superfamily, regulates cell growth and function through numerous signalling pathways. This project will provide structural information about IGFBP-3 as a protot ....Structural elucidation and functional analysis of insulin-like growth factor binding protein-3 domains. Translating information from the human genome project into information about cell function is a major challenge in the post-genome era. The multifunctional insulin-like growth factor binding protein-3 (IGFBP-3), a member of a multigene superfamily, regulates cell growth and function through numerous signalling pathways. This project will provide structural information about IGFBP-3 as a prototype for the superfamily, and using a combination of methodologies will unravel mechanisms of IGFBP-3 action. The project will advance understanding of IGFBP-3 and superfamily functions, and provide both benefits in international research leadership and economic and health benefits in animal and human growth and metabolism.Read moreRead less
New Techniques for Structural Biology and Directed Molecular Evolution. This PhD program will equip an Australian graduate with advanced training in techniques in molecular genetics and protein chemistry that are currently in high demand by the biotechnology industry, and also provide him/her with direct experience of an industrial R&D laboratory environment. Moreover, it will establish a basis for further collaboration between a leading University-based research laboratory and an established R& ....New Techniques for Structural Biology and Directed Molecular Evolution. This PhD program will equip an Australian graduate with advanced training in techniques in molecular genetics and protein chemistry that are currently in high demand by the biotechnology industry, and also provide him/her with direct experience of an industrial R&D laboratory environment. Moreover, it will establish a basis for further collaboration between a leading University-based research laboratory and an established R&D company that will lead to development of new techniques for use in biotechnology in Australia and overseas.Read moreRead less
How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by wh ....How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by which clusterin effects its protective actions. We expect to demonstrate that clusterin protects cells form stresses by exerting its chaperone action at or near the cell surface and to identify specific regions and structural features of the clusterine molecule important in its chaperone action.Read moreRead less