Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a mo ....Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a model for epigenetic change, and sex chromosomes, which has engaged some of the greatest genetic minds over nearly a century. Therefore my results will attract wide international interest and impact positively on Australia's scientific profile, and further highlight the importance of Australian mammals.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.Read moreRead less
Ethical and Social Issues in Translating Epigenetics into Antenatal Care. This project aims to investigate how knowledge about the intergenerational transmission of health and disease is shaping antenatal care in Australia. It expects to generate new knowledge about how the science of epigenetics can be used to address social inequality and is anticipated to have impact across the social sciences, bioethics and public health. Expected outcomes of the project include novel theoretical approaches ....Ethical and Social Issues in Translating Epigenetics into Antenatal Care. This project aims to investigate how knowledge about the intergenerational transmission of health and disease is shaping antenatal care in Australia. It expects to generate new knowledge about how the science of epigenetics can be used to address social inequality and is anticipated to have impact across the social sciences, bioethics and public health. Expected outcomes of the project include novel theoretical approaches to the ethics of pregnancy, along with guidance tools to shape the use of epigenetics in antenatal care and social policy to reduce social inequalities. This should provide significant benefits, improving information and support available to vulnerable women as they negotiate maternal health and social services. Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less
Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown t ....Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown to respond to mechanical stimuli in the same manner as mechanoreceptor channels of organisms from bacteria to humans the intended outcome of this project is to uncover the unifying principles of mechanotransduction anchored in the laws of physics and chemistry that have guided the force-dependent design of all life forms.Read moreRead less
Multifunctional trilayer separator for durable multivalent energy storage. This project aims to develop an important new family of economical, high energy, multivalent batteries based on an abundant element, sulphur. The project plans to design a new battery separator to enable long-term stability in sulphur-based rechargeable batteries. This type of separator is of critical importance in many membrane-involved energy storage technologies. The project plans to use leading-edge durable energy tec ....Multifunctional trilayer separator for durable multivalent energy storage. This project aims to develop an important new family of economical, high energy, multivalent batteries based on an abundant element, sulphur. The project plans to design a new battery separator to enable long-term stability in sulphur-based rechargeable batteries. This type of separator is of critical importance in many membrane-involved energy storage technologies. The project plans to use leading-edge durable energy technologies to strengthen the development of residential energy systems and the involvement of renewable energy sources in modern grid.Read 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