Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success ....Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success and health of offspring. The outcomes will inform development of new diagnostic assays for male fertility, and underpin strategic design of novel fertility treatments and products with applications in the human health and animal breeding industries. Read moreRead less
Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and c ....Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and cutting-edge directed evolution methodologies. Intended outcomes include enhanced institutional capacity for interdisciplinary collaboration; discovery of fundamentally important bacterial sensors; and development of synthetic regulatory circuits enabling outgrowth of non-biological biocatalysis industries.Read moreRead less
Site-specific protein functionalisation at diselenides via photocatalysis . This project aims to develop a new photocatalytic reaction for the on demand functionalisation of proteins. The synthetic methodology will solve a major technological gap in the field by enabling efficient access to proteins with defined modifications at specific locations. Functionalised proteins generated in the project will underpin a detailed understanding of how specific modifications influence the structure and fun ....Site-specific protein functionalisation at diselenides via photocatalysis . This project aims to develop a new photocatalytic reaction for the on demand functionalisation of proteins. The synthetic methodology will solve a major technological gap in the field by enabling efficient access to proteins with defined modifications at specific locations. Functionalised proteins generated in the project will underpin a detailed understanding of how specific modifications influence the structure and function of several important proteins. The project will generate significant new knowledge in the fields of chemistry and biology and will foster interdisciplinary collaboration, nationally and internationally. The breakthrough technology also has the potential to benefit Australia’s biotechnology sector.Read moreRead less
A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough ....A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough and responsive hydrogel platform from this disordered protein family through greater understanding of structure and mechanical function and incorporating adequate stiffness, strength and biocompatibility. Such tough hydrogels would be applicable to a range of biotechnological applications (eg intervertebral disc repair or artificial skin tissue engineering).Read moreRead less
Interactions between cells and extracellular matrix in the epithelial-mesenchymal transition of the ovarian follicular stratified epithelium. The lining of many mammalian organs and cavities contain cells that can transform into different cells to bring about organ development or repair but if it goes horribly wrong the cells become metastatic cancers. This project examines the key features of this process especially the roles of matrix that develops around the cells in this process.
Bio-inspired molecular electronics: from nanoscience to nanotechnology. This project aims to investigate electron transport in naturally occurring peptides, while exploiting their electronic properties to promote the design and development of functional bio-inspired molecular electronic devices. Molecular electronics is at the forefront of international interdisciplinary research, with its significance and necessity stemming from the inevitable physical limitations of existing silicon-based elec ....Bio-inspired molecular electronics: from nanoscience to nanotechnology. This project aims to investigate electron transport in naturally occurring peptides, while exploiting their electronic properties to promote the design and development of functional bio-inspired molecular electronic devices. Molecular electronics is at the forefront of international interdisciplinary research, with its significance and necessity stemming from the inevitable physical limitations of existing silicon-based electronics. This project aims to establish a foundation to advance fundamental knowledge in this area, which will lead to the design and development of functional bio-inspired molecular electronic devices.Read moreRead less
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Male to female sperm signalling – a new role for sperm in reproduction? Male seminal fluid is commonly thought simply to provide sperm for conception. This project aims to investigate a lesser known action of sperm: modifying the female immune response to increase the chances of reproductive success. The project aims to define the molecular pathway through which sperm interact with female cells, particularly how B-defensins on sperm bind to Toll-like receptors to stimulate female immune toleranc ....Male to female sperm signalling – a new role for sperm in reproduction? Male seminal fluid is commonly thought simply to provide sperm for conception. This project aims to investigate a lesser known action of sperm: modifying the female immune response to increase the chances of reproductive success. The project aims to define the molecular pathway through which sperm interact with female cells, particularly how B-defensins on sperm bind to Toll-like receptors to stimulate female immune tolerance. The project plans to use embryo transfer and genetic mouse models to determine the physiological benefit of sperm signalling. Evidence that seminal fluid signalling operates in mammals to ensure optimal female reproductive investment would advance knowledge of the male contribution to the reproductive process.Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less