Molecular basis of antimicrobial and insecticidal activity of floral defensins from the Solonaceae. The flowers of Solanaceous plants produce high levels of defensins that protect the reproductive tissues against potential damage from microorganisms. The presence of related defensins in mammals, insects and plants indicates that they are part of an ancient defence mechanism. The floral defensins are potent antifungal molecules and surprisingly also have insecticidal activity. The aim of this pro ....Molecular basis of antimicrobial and insecticidal activity of floral defensins from the Solonaceae. The flowers of Solanaceous plants produce high levels of defensins that protect the reproductive tissues against potential damage from microorganisms. The presence of related defensins in mammals, insects and plants indicates that they are part of an ancient defence mechanism. The floral defensins are potent antifungal molecules and surprisingly also have insecticidal activity. The aim of this project is to understand the molecular basis of the antifungal and insecticide activity and to use this knowledge to produce improved molecules for crop protection.Read moreRead less
Searching for novel protein domains: A bioinformatic analysis of whole proteomes. The functional annotation of the set of proteins encoded by a whole genome (the "proteome") is a crucial component of genome research. The aim of this project is to extend the functional and structural annotation of large protein databases by identifying novel protein domain families and building a novel domain library. Our approach is semi-automated and fast, thanks to execution in the fastest parallel supercom ....Searching for novel protein domains: A bioinformatic analysis of whole proteomes. The functional annotation of the set of proteins encoded by a whole genome (the "proteome") is a crucial component of genome research. The aim of this project is to extend the functional and structural annotation of large protein databases by identifying novel protein domain families and building a novel domain library. Our approach is semi-automated and fast, thanks to execution in the fastest parallel supercomputer in Australia available at the Victorian Partnership for Advanced Computing. Our preliminary data demonstrates that our method is feasible.Read moreRead less
Autophagy and the nucleus. Autophagy is a degradation pathway that is essential for survival, internal change (differentiation and development) and maintenance of physiological equilibrium (homeostasis). Moreover autophagy serves to protect higher organisms against infections, cancer and neurodegeneration. This project seeks to better understand the mechanisim by which parts of the nucleus can be degraded by autophagy and how this relates to diseases which may involve defects in, or abnormal deg ....Autophagy and the nucleus. Autophagy is a degradation pathway that is essential for survival, internal change (differentiation and development) and maintenance of physiological equilibrium (homeostasis). Moreover autophagy serves to protect higher organisms against infections, cancer and neurodegeneration. This project seeks to better understand the mechanisim by which parts of the nucleus can be degraded by autophagy and how this relates to diseases which may involve defects in, or abnormal degradation of nuclear components. Benefit will accrue from a contribution to knowledge with future potential to impact on disease, as well as strengthening links with the international network working in the field of autophagy.Read moreRead less
Development of high-throughput in silico methods for protein structure determination by X-ray crystallography. This work will have major outcomes for structural biology research at a national and international level. The ability to perform MR calculations using an exhaustive set of search models will offer a timesaving of weeks to months in a typical successful structure determination. Further, significant insights will be gained into the use of high-performance GRID computing in protein struct ....Development of high-throughput in silico methods for protein structure determination by X-ray crystallography. This work will have major outcomes for structural biology research at a national and international level. The ability to perform MR calculations using an exhaustive set of search models will offer a timesaving of weeks to months in a typical successful structure determination. Further, significant insights will be gained into the use of high-performance GRID computing in protein structure determination by X-ray crystallography. This knowledge has considerable impact on our ability to undertake high quality structural biology research - a key area in the majority of biological research programmes. Read moreRead less
Structural and Functional studies on Membrane Attack Complex / Perforin-like proteins. Membrane Attack Complex Perforin (MACPF) proteins play crucial roles in immunity and development. Together, these molecules comprise the largest family of pore forming proteins in eukaryotes. This proposal will result in a major advancement of knowledge in our understanding of the MACPF mechanism of pore formation. These data will provide fundamental insight into how proteins can change shape and adopt both wa ....Structural and Functional studies on Membrane Attack Complex / Perforin-like proteins. Membrane Attack Complex Perforin (MACPF) proteins play crucial roles in immunity and development. Together, these molecules comprise the largest family of pore forming proteins in eukaryotes. This proposal will result in a major advancement of knowledge in our understanding of the MACPF mechanism of pore formation. These data will provide fundamental insight into how proteins can change shape and adopt both water-soluble and membrane bound states. Our work will also eventually be important in developing approaches to control unwanted MACPF function, for example in diabetes or transplant rejection. Finally, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Application of direct protein transduction of Stem Cell Factors to reprogram mouse and human somatic cells into pluripotent stem cells. This project aims to generate embryonic stem cell-like cells from human somatic cells, using direct protein transduction of defined factors, rather than through retroviral delivery. This will bring stem cell application closer to a therapeutic setting. The cells produced will be free from genetic modification and will yield products for patient-specific cell-ba ....Application of direct protein transduction of Stem Cell Factors to reprogram mouse and human somatic cells into pluripotent stem cells. This project aims to generate embryonic stem cell-like cells from human somatic cells, using direct protein transduction of defined factors, rather than through retroviral delivery. This will bring stem cell application closer to a therapeutic setting. The cells produced will be free from genetic modification and will yield products for patient-specific cell-based therapies that will be accepted by recipients without the need for immunosuppressant therapy. This development is expected to revolutionize the current approach to treating disease and injury, and is likely to result in the generation of highly marketable potent cell reprogramming therapeutics.Read moreRead less
Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four ne ....Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four neuronal cell cultures established with gene-based selection criteria. These cultures will be characterised by gene expression, immunocytochemistry, radiolabelled neurotransmitter release, electrophysiology and Ca2+ imaging studies. This study will highlight the functional effects of gene selection procedures upon stem cell-derived neurons.Read moreRead less
Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, ....Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, for example in disease such as diabetes or transplant rejection. Furthermore, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits wi ....A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits within the complex, or between ATP synthase and other enzyme complex involved in energy production (including other ATP synthase complexes) will be investigated. New and significant insights into one of the most fundamental and challenging enzymes of life will be obtained.Read moreRead less