Complex Multiscale Systems: Modeling, Analysis and Scientific Computation. This project aims to develop and implement a systematic approach, both analytic and computational, to extract compact, accurate, system level models of complex physical and engineering systems. The wide ranging methodology is to construct computationally efficient "wrappers" around fine scale, microscopic, detailed descriptions of dynamical systems (particle or molecular simulation, or partial differential equations or la ....Complex Multiscale Systems: Modeling, Analysis and Scientific Computation. This project aims to develop and implement a systematic approach, both analytic and computational, to extract compact, accurate, system level models of complex physical and engineering systems. The wide ranging methodology is to construct computationally efficient "wrappers" around fine scale, microscopic, detailed descriptions of dynamical systems (particle or molecular simulation, or partial differential equations or lattice equations). Comprehensively accounting for multiscale interactions between subgrid processes among macroscale variations ensures stability and accuracy. Based on dynamical systems theory and analysis, this approach is expected to empower systematic analysis and understanding for optimal macroscopic simulation for forthcoming exascale computing.Read moreRead less
Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsi ....Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsis of plant stress response. This will be achieved using new high-throughput technologies, allowing reliable qualitative and quantitative analysis of large numbers of samples. This approach will compliment existing genomic and proteomic analyses of plants exposed to abiotic stress.Read moreRead less
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less
Ultra-high spectral purity lasers for tests of relativity and atomic clocks. Measurement precision is the key to advancement of a technological society. This project aims to build the most precise measurement tool ever developed: one capable of delivering 17 digits of precision in just 1 second. In conjunction with German and French colleagues this too will be used to test the foundation theories of physics.
Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to un ....Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to unravel the mechanistic basis of the reproductive lesion in TGFb1 null mutant mice and to determine the effect of exogenous systemic delivery of TGFb1 in alleviating this lesion. It is expected that the project will provide new insight into key roles for TGFb1 in governing male and female fertility, and shed light on the prospects for exogenous supplementation of TGFb1 for improving reproductive performance in wild-type animals. This knowledge has potentially important applications in the livestock breeding industry, in devising novel contraceptive vaccine strategies, in the human pharmaceutical industry, and in devising novel contraceptive vaccine strategies.Read moreRead less
Yeast cell-cell communication of overcrowding and nutrient limitation: novel signalling systems and their impact on fermentation. The project will investigate known and novel signalling molecules that allow communication between yeast cells and impact on fermentation dynamics, specifically in a nutrient-depleted environment. The mechanisms by which these molecules exert their effect will be defined using a systems biology approach that integrates many analyses and data sets.
TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system ....TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system that can precisely control different aspects of the toolbox performance to understand this process. The knowledge and resources generated can be used to develop products or services with tangible economic and health benefits.Read moreRead less
The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progress ....The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progression. The work will contribute to the training of one or more graduate students in a technologically advancing and internationally competitive field.Read moreRead less
Gating and permeation in ClC channels. Chloride ion channels are essential proteins in all living cells but, compared to other channels, little is known of their structure or how this defines and controls chloride transport. We will produce both normal and structurally modified (mutant and known to cause disease) chloride channels in cultured cells by genetic engineering so that we can analyse channel function using a combination of electrophysiological and chemical methods. We expect to learn ....Gating and permeation in ClC channels. Chloride ion channels are essential proteins in all living cells but, compared to other channels, little is known of their structure or how this defines and controls chloride transport. We will produce both normal and structurally modified (mutant and known to cause disease) chloride channels in cultured cells by genetic engineering so that we can analyse channel function using a combination of electrophysiological and chemical methods. We expect to learn which channel parts are fundamental and how subtle changes in structure can alter the opening and closing of these channels and the way that chloride passes through them.Read moreRead less