SCP/TAPS proteins of the barber’s pole worm. This integrated, collaborative project, will explore, in a targeted way, the structure and function of a key group of molecules in a socio-economically important eukaryotic pathogen and their involvement in pathogen-host interactions. Fundamental knowledge and understanding of these molecules will provide a solid foundation for understanding disease processes and finding new intervention strategies for a range of pathogens. This is crucial, given the ....SCP/TAPS proteins of the barber’s pole worm. This integrated, collaborative project, will explore, in a targeted way, the structure and function of a key group of molecules in a socio-economically important eukaryotic pathogen and their involvement in pathogen-host interactions. Fundamental knowledge and understanding of these molecules will provide a solid foundation for understanding disease processes and finding new intervention strategies for a range of pathogens. This is crucial, given the serious drug resistance problems in pathogens, and residue problems in meat, milk and the environment.Read moreRead less
Infrakingdom Alveolata: searching for a defining structural feature. This project will establish the first molecular nexus between a cellular structure currently used to define an Infrakingdom of life. It will aid in the higher order systematics of our microscopic diversity and allow us to interpret how important parasites learned to penetrate host cells to establish infection. We will train excellent graduate and Honours students in cellular and molecular biology.
Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theo ....Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theory. This should help to rationalise and direct funding supplied to these areas. The second benefit is for Australia: aging is a fruitful area for research because of the high general public interest and for training because of its multidisciplinary nature, and funding in Australia is very low by international standards. Read moreRead less
Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the st ....Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the structure of membrane proteins are difficult to determine and the newly developed techniques used for the structural determination of this membrane-associated protein will be suitable for studying other membrane proteins and receptors of pharmaceutical importance.Read moreRead less
Probing membrane rafts using surface-selective multi-dimensional microscopy. The results of this project will provide fundamental insights into the role played by domains in cell membranes in the regulation of membrane protein function. These insights will create new avenues in the biotechnology industry for development of novel therapeutics aimed at disruption of membrane protein-protein interactions that cause aberant cell signalling in disease states such as cancer.
Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous e ....Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous experimental test. Empirical verification of this theory will pave the way to elucidating the functional importance of large scale brain electrical activity in neural information processing as well as enabling the rational use of the EEG for drug design and diagnosis.Read moreRead less
Understanding responses to climate change: a mechanistic approach integrating functional genetics, physiology and biophysical models for the Common brown butterfly. We will dissect the interaction between an Australian butterfly and changing climate. This will make significant contributions to the national research priorities Responding to climate change and variability and Sustainable use of Australia's biodiversity. We will address the known deficits in standard approaches to predicting futu ....Understanding responses to climate change: a mechanistic approach integrating functional genetics, physiology and biophysical models for the Common brown butterfly. We will dissect the interaction between an Australian butterfly and changing climate. This will make significant contributions to the national research priorities Responding to climate change and variability and Sustainable use of Australia's biodiversity. We will address the known deficits in standard approaches to predicting futures for biota. We will provide an Australian species in which the mechanisms of response to climate change are understood in detail. Our outputs will be directly applicable to other butterflies: 19 threatened taxa in Australia. The novelty of our approach will be of marked international interest, and will train Australian researchers in a new way of predicting biological impacts of climate change.Read moreRead less
Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease. A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. The key protein causing AD is Abeta and characterization of the toxic species of this peptide is critical towards identifying potential therapeutic targets. This proposal aims to study mut ....Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease. A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. The key protein causing AD is Abeta and characterization of the toxic species of this peptide is critical towards identifying potential therapeutic targets. This proposal aims to study mutant peptides made synthetically and to identify a membrane-binding site. By establishing which lipid is critically involved in membrane binding of Abeta and mediating subsequent cell death, drugs may be developed to prevent the binding of Abeta to membranes resulting in neuronal survival and prevention of memory loss in AD patients.Read moreRead less
The flow properties of proteins and other biopolymers. The living cell is an extraordinary organization with a vast variety of biomacromolecules carrying out myriads of functions with great specificity and accuracy. The key issue in cell biology is to unravel the structures of biopolymers and the deep connection that exists between structure and function. This interdisciplinary research program combines recent advances in experimental and theoretical rheology, with advances in protein science, t ....The flow properties of proteins and other biopolymers. The living cell is an extraordinary organization with a vast variety of biomacromolecules carrying out myriads of functions with great specificity and accuracy. The key issue in cell biology is to unravel the structures of biopolymers and the deep connection that exists between structure and function. This interdisciplinary research program combines recent advances in experimental and theoretical rheology, with advances in protein science, to investigate the response of biopolymers to deformation. This approach will lead to insights into the problem of protein folding, the interaction of biopolymers with surfaces, and the physical basis for the mechanical properties of biopolymers.Read moreRead less
Optical manipulation of single molecules in nanocontainers and nanotubes. Modern medicine has benefited greatly from technological advances in instrumentation. The ability to probe and manipulate new aspects of biological function often provides unique information that can be used as the basis of new medical treatments. Recent advances in optical instrumentation and biochemical labelling has enabled the study of biological function at the single molecule level. This project proposes to develop n ....Optical manipulation of single molecules in nanocontainers and nanotubes. Modern medicine has benefited greatly from technological advances in instrumentation. The ability to probe and manipulate new aspects of biological function often provides unique information that can be used as the basis of new medical treatments. Recent advances in optical instrumentation and biochemical labelling has enabled the study of biological function at the single molecule level. This project proposes to develop new techniques in single molecule manipulation, to perform studies not easily addressable using current techniques. The proposed research will form the basis of an enabling technology for Australian researchers to make breakthroughs in biomedical research, potentially leading to improvements in healthcare.Read moreRead less