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
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.
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
Defining peptide structure and function: the shape of things to come. In this project we develop new and general ways of chemically defining the structure and function of natural peptides. This then provides a basis of potential therapies to treat a number of diseases currently confronting Australia's aging population, for example, cataract, Alzheimer's disease, cancer, and cardiovascular disease.
Small heat-shock molecular chaperone proteins and amyloid fibrils. This proposal addresses the fundamental mechanisms of protein aggregation associated with debilitating age-related diseases, e.g. Alzheimer's, Parkinson's and cataract, and the prevention of aggregation via the action of a group of molecular chaperone proteins known as small heat-shock proteins. With the ageing population, the prevalence of these diseases will increase significantly over the next 20 years. Understanding and treat ....Small heat-shock molecular chaperone proteins and amyloid fibrils. This proposal addresses the fundamental mechanisms of protein aggregation associated with debilitating age-related diseases, e.g. Alzheimer's, Parkinson's and cataract, and the prevention of aggregation via the action of a group of molecular chaperone proteins known as small heat-shock proteins. With the ageing population, the prevalence of these diseases will increase significantly over the next 20 years. Understanding and treating these diseases will therefore have significant long-term health benefits. Furthermore, the highly structured protein aggregates that form as hallmarks of many of these diseases have potential wide ranging applications in the emerging field of bionanotechnology, e.g. as nanowires and biofilms.Read moreRead less
Vortex fluidic mediated chemical transformations. This project aims to develop a continuous flow vortex fluidic device (VFD) for chemical and biochemical transformations. Vortex fluidic devices should lead to cleaner and faster ways of preparing complex molecules. Depending on the VFD’s operating parameters, including applying field effects such as Faraday waves, plasmas and light sources, reactions could have higher yields and selectivity than traditional batch processing. This will be translat ....Vortex fluidic mediated chemical transformations. This project aims to develop a continuous flow vortex fluidic device (VFD) for chemical and biochemical transformations. Vortex fluidic devices should lead to cleaner and faster ways of preparing complex molecules. Depending on the VFD’s operating parameters, including applying field effects such as Faraday waves, plasmas and light sources, reactions could have higher yields and selectivity than traditional batch processing. This will be translated into molecular assembly line syntheses in a single unit or a series. Such syntheses should provide a versatile toolbox for molecular transformations, under continuous flow conditions where scalability is addressed upfront. This will be attractive to industry and minimise effects on the environment.Read moreRead less
Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens ....Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens of which account for billions of dollars and millions of Australians. This project aims to understand one of the major mechanisms that controls cell migration, which is expected to produce significant economic and social outcomes in the areas of basic science knowledge, human health, and biotechnology. Read moreRead less