Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mil ....Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mild conditions by enzymes termed nitrilases. We will work on fungal nitrilases as they present a globally attractive, yet untapped commercial target. The outcome for Applimex will be a suite of biocatalysts specific for the production of key intermediates for drug and agrochemical syntheses.Read moreRead less
Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein ....Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein quality control in the cell to take advantage of the global opportunities that recombinant gene expression indisputably offers in the form of unrestricted supply of proteins of social and economic value. The project will create novel IP and licensing opportunities for Australia.Read moreRead less
Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzy ....Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzyme. This project describes the biochemical characterisation of specific enzyme activities within microcystin synthetase and how they determine the final structure and toxicity of the many forms of microcystin. Interactions between this enzyme complex and its substrate amino acids will provide information for the genetic engineering of this and similar natural products.Read moreRead less
Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology re ....Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology research in Australia. The project anticipates contributing to new tools for delivering genes to cells, benefiting therapeutic and biotechnology applications.Read moreRead less
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding ....Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes. Expected Outcomes and Benefits: This proposal will provide novel targets and methodology for gene modulation with broad applications from biology to environmental sciences.Read moreRead less
Single cell glycomics: mapping the surface glycan signature of cells. This project aims to develop a platform technology for multiplexed glycan mapping of the surface of a single cell to address challenges of functional glycomics by utilising a conceptually new approach. By combining newly designed plasmonic nanoparticles with surface-enhanced Raman scattering tags and multiple specific carbohydrate-recognising lectins, this project expects to produce a generic technology that is capable of non- ....Single cell glycomics: mapping the surface glycan signature of cells. This project aims to develop a platform technology for multiplexed glycan mapping of the surface of a single cell to address challenges of functional glycomics by utilising a conceptually new approach. By combining newly designed plasmonic nanoparticles with surface-enhanced Raman scattering tags and multiple specific carbohydrate-recognising lectins, this project expects to produce a generic technology that is capable of non-destructive barcoding of the surface glycan signature of single cells in their native state and in response to metabolic perturbations. Expected project outcomes include advancing knowledge in nanobiotechnology, glycobiology and cell biology by being able to easily monitor changes to the surface of single cells.Read moreRead less
Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolut ....Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolution of live imaging to the single molecule to understand the dynamics of actin assembly with implications for cellular processes that are hijacked in diseases. It also aims to provide a novel assay that may enable testing of the impact of drugs on cellular processes in real time.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
Industrial Transformation Training Centres - Grant ID: IC200100052
Funder
Australian Research Council
Funding Amount
$4,789,838.00
Summary
ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide signifi ....ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide significant benefits including advancing Australian biotechnological capacity and improved linkages with major pharmaceutical partners. It should also provide a substantive competitive advantage to nascent Australian biotechnology companies that also links into new National investment into drug discovery and development infrastructure.Read moreRead less