Mathematical Methods for Next Generation Sequencing. The emergence of a new generation of high throughput genomic sequencing technologies is providing unprecedented opportunities for biological research. Hidden within the huge amounts of data generated by this technology is information about the expression and regulation of genes, and the complex functional purpose of non-coding, so called 'junk', DNA. Development of mathematical and statistical tools is essential to interpreting these data. The ....Mathematical Methods for Next Generation Sequencing. The emergence of a new generation of high throughput genomic sequencing technologies is providing unprecedented opportunities for biological research. Hidden within the huge amounts of data generated by this technology is information about the expression and regulation of genes, and the complex functional purpose of non-coding, so called 'junk', DNA. Development of mathematical and statistical tools is essential to interpreting these data. The proposed research will enhance Australia's reputation for developing novel quantitative techniques at the cutting edge of modern biology. The proposed project has a broad range of potential applications in biotechnology, particularly in the medical and agricultural industries.Read moreRead less
A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us und ....A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us understand the distribution and diversity of these organisms in relation to global primary productivity. They will also lead to the development of more robust biomarkers for metal stress and pollution in coastal environments.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
Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights ....Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights into endosomal trafficking at the molecular level. Outcomes from this work will place Australia at the forefront of international efforts to understand this essential biological process and will have important implications for future design of pharmaceuticals.Read moreRead less
TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation. Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protei ....TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation. Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protein, as constrained and selected by evolution. The question is how do they work? Answering this requires energetic and thermodynamic analysis beyond current experimental techniques, but accessible by computer simulation. We aim to develop a robust toolkit of simulation methods and protocols, blind test them by predicting the mechanism of a new enzyme, with followup experimental validation.
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Characterization and optimisation of Myomatrix: A novel extracellular matrix hydrogel from muscle. This project would have several sources of benefit for the community. Foremost we will have produced a product that will have a strong commercial application in several fields including basic science and bioengineering. If its full potential were achieved, the development of this innovative new hydrogel would strengthen Australia's standing in the biotechnology field and also enrich specific applic ....Characterization and optimisation of Myomatrix: A novel extracellular matrix hydrogel from muscle. This project would have several sources of benefit for the community. Foremost we will have produced a product that will have a strong commercial application in several fields including basic science and bioengineering. If its full potential were achieved, the development of this innovative new hydrogel would strengthen Australia's standing in the biotechnology field and also enrich specific applications. The knowledge gained from the characterization of this product could also be of benefit to several areas including chemical engineering, tissue engineering, tissue repair, polymer chemistry and food manufacture. The expertise generated and the possibility of collaboration, both academic and with industry would also benefit the community. 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
Kingdom switching microbial pathogens: the bioinformatics of mutation in the genomes of viruses and bacteria affecting crops, livestock and people. Some organisms that cause infectious diseases have moved between plants and vertebrates, either recently or repeatedly over evolutionary time. Switching between plants and vertebrates strongly influences the way these microbes mutate and evolve. We will search the genomic sequence databases for information about how the choice of host influences muta ....Kingdom switching microbial pathogens: the bioinformatics of mutation in the genomes of viruses and bacteria affecting crops, livestock and people. Some organisms that cause infectious diseases have moved between plants and vertebrates, either recently or repeatedly over evolutionary time. Switching between plants and vertebrates strongly influences the way these microbes mutate and evolve. We will search the genomic sequence databases for information about how the choice of host influences mutations in viral and bacterial genomes and model the evolutionary processes involved. This project will advance our understanding of the fine structure of microbial genomes and the importance of selection pressures on genes. It will lead to better disease management strategies for humans, and for domestic crops and livestock.Read moreRead less
Theoretical and experimental studies on magnetoelectroelastic bone remodelling process. The project combines biotechnology and material science which will have national economic, social and environment impact. It can benefit industry by providing knowledge that help scientists understand remodeling under coupled fields and is used to develop bone replacement. By better understanding remodeling due to multi-field loading, we can assist scientists in aeronautical industry in developing countermeas ....Theoretical and experimental studies on magnetoelectroelastic bone remodelling process. The project combines biotechnology and material science which will have national economic, social and environment impact. It can benefit industry by providing knowledge that help scientists understand remodeling under coupled fields and is used to develop bone replacement. By better understanding remodeling due to multi-field loading, we can assist scientists in aeronautical industry in developing countermeasures that reduce or eliminate bone loss resulting from long-duration space flight. It can provide knowledge that can be used to explore underlying mechanisms controlling bone remodeling and self-repair in gaining insight into debilitating diseases such as osteoporosis, to develop high-performance prosthetics for medical injury healing.Read moreRead less
New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein i ....New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein interaction sites and characterization of protein motions. The limits of NMR spectroscopy will be pushed to analyse systems of significantly increased molecular weights. The project includes applications to drug targets such as the dengue virus NS2B/NS3 protease.Read moreRead less