A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conduct ....A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conductance properties of the channel. Accurately
determining these relationships provides a pathway to developing cures
for many neurological, cardiac, and muscular diseases.
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Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the de ....Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the design of novel compounds for treating muscle disorders in animals and humans, for improving meat quality and for use as insecticides. The project will facilitate graduate and undergraduate training in basic science with exposure to biotechnology, through our commercial partner Biotron.Read moreRead less
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology. The CoE in Convergent Bio-Nano Science &Technology comprises a multi-disciplinary team focused on research aiming to understand and control the interface of materials with biological systems. The Centre will exploit knowledge of the bio-nano interface to design materials that transport and deliver vaccines, drugs and gene therapy agents, and to design new diagnostic agents and devices. Nanomedicines are on the cusp of revol ....ARC Centre of Excellence in Convergent Bio-Nano Science and Technology. The CoE in Convergent Bio-Nano Science &Technology comprises a multi-disciplinary team focused on research aiming to understand and control the interface of materials with biological systems. The Centre will exploit knowledge of the bio-nano interface to design materials that transport and deliver vaccines, drugs and gene therapy agents, and to design new diagnostic agents and devices. Nanomedicines are on the cusp of revolutionizing diagnosis and therapy in many diseases. The CoE will be the focus of bio-nano research activity in Australia, uniting universities, research agencies, institutes and companies. The expected outcomes are better diagnostic and therapeutic tools designed via an enhanced understanding of the bio-nano-interface.Read moreRead less
Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new gene ....Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new genes on all ten sex chromosomes and investigate how they determine sex. The set up of an Australian Monotreme Resource Centre will be crucial for this research and attract worldwide high profile collaborations. We will answer important general questions in monotreme biology and contribute to our understanding of sexual abnormalities in humans.Read moreRead less
Sequence to Sequence: Rigorous Statistical and Mathematical Analysis of Biological Sequence Data. Comparative genomics is fundamental for developing an understanding of genes and their function. For example, using statistical and computational techniques, it was recently demonstrated that 60% of genes are conserved between fly and human. When the human gene that confers susceptibility to Parkinson's disease was transferred into the fly it caused symptoms similar to those seen in humans. The futu ....Sequence to Sequence: Rigorous Statistical and Mathematical Analysis of Biological Sequence Data. Comparative genomics is fundamental for developing an understanding of genes and their function. For example, using statistical and computational techniques, it was recently demonstrated that 60% of genes are conserved between fly and human. When the human gene that confers susceptibility to Parkinson's disease was transferred into the fly it caused symptoms similar to those seen in humans. The future development of 'personalized medicine' will rely upon understanding the function of human genes, as will progress in the agricultural sector. Rigorous statistical analysis and development of appropriate bioinformatic methods are crucial to biological sequence analysis in comparative genomics.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Statistical Advances in the Post-Genome Era. Biologically relevant statistical foundations for post-genome biology and biotechnology will be developed. Specific goals of the topics include the development of accurate and more efficient algorithms for sequence alignments, improved models to maximise the accuracy of analyses for gene expression data and superior statistical methods for identification of complex gene networks that predispose an organism to disease. The Project will make significant ....Statistical Advances in the Post-Genome Era. Biologically relevant statistical foundations for post-genome biology and biotechnology will be developed. Specific goals of the topics include the development of accurate and more efficient algorithms for sequence alignments, improved models to maximise the accuracy of analyses for gene expression data and superior statistical methods for identification of complex gene networks that predispose an organism to disease. The Project will make significant contributions to the new and evolving priority research area of Bioinformation Science (including bioinformatics). Outcomes will include novel techniques for analysis and mining of post-genome data, with applications to developments in Bio-medicine and Bio-agricultureRead moreRead less
The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.Read moreRead less
Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pa ....Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pathogenic behaviour and biomass production.Read moreRead less
Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is ....Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is to elucidate how genes are assembled into complex active or inactive chromatin structures by employing a novel in vitro system. This information will have important implications for gene therapy strategies.
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