The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along ....The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along with a novel methodology for validating mathematical models against experimental data. These innovations offer a completely fresh approach to identifying and modulating the adaptive capacities of living cells, which may contribute to overcoming the problem of drug resistance in future therapeutic development.
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Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artifi ....The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artificial regulation of the ribosome may also emerge, relevant to synthetic biology and the engineering of industrial yeasts. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.Read moreRead less
The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic c ....The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic cell recirculation, and what consequences the recirculation has for immune cell function. This understanding will significantly advance our basic understanding of the immune system.Read moreRead less
Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic fr ....Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic framework. This should provide major benefits for understanding bacterial ecology and evolution, and for future studies seeking to optimise industrial processes or prevent disease. It will also directly contribute to building Australia’s capacity in computational biology- a key driver of biotechnology innovation.Read moreRead less
Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dime ....Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dimension reduction multivariate method developments for data integration. By combining in silico and in vivo approaches, the project is anticipated to benefit scientists willing to work in cutting-edge single-cell research by providing useful protocols and tools to generate novel insights in cell biology. Read moreRead less
Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
Formation of boundaries in the developing embryo. This project aims to decipher how the boundaries between the different organs are established in the developing embryo. The project aims to identify the components of the gene regulatory network that controls lateral plate mesoderm formation, develop a mathematical model that can explain how the domains are formed within this region, and validate novel interactions in vivo in zebrafish. The expected outcome of the project is to reveal how the pro ....Formation of boundaries in the developing embryo. This project aims to decipher how the boundaries between the different organs are established in the developing embryo. The project aims to identify the components of the gene regulatory network that controls lateral plate mesoderm formation, develop a mathematical model that can explain how the domains are formed within this region, and validate novel interactions in vivo in zebrafish. The expected outcome of the project is to reveal how the progenitors of our body parts are instructed to be positioned at the right time and at the right place in the embryo. This project should provide significant benefit such as the expansion of Australia's knowledge base and research capability in cross-disciplinary science.Read moreRead less
Developing bioinformatics methods for single cell transcriptomics. This project aims to develop novel bioinformatics methods for single cell transcriptomic data that seek to model variability in cell populations. The project expects to generate new approaches using Bayesian statistics that will act as high-end enablers of discovery in transcriptional regulatory processes. Through an interdisciplinary combination of experimental and computational research, insights into fundamental biological pro ....Developing bioinformatics methods for single cell transcriptomics. This project aims to develop novel bioinformatics methods for single cell transcriptomic data that seek to model variability in cell populations. The project expects to generate new approaches using Bayesian statistics that will act as high-end enablers of discovery in transcriptional regulatory processes. Through an interdisciplinary combination of experimental and computational research, insights into fundamental biological processes will be elucidated, specifically the robustness of cellular systems. Expected outcomes include a suite of novel tools that will push the boundaries of current bioinformatics solutions with potential to deliver significant benefits to every domain of biological science, particularly tissue engineering and synthetic biology.Read moreRead less
Characterization of the dark metabolome of eukaryotic cells. The project aims to investigate the full metabolic potential of a group of eukaryotic organisms using advanced analytical and computational techniques. It will identify novel metabolites and enzyme activities that are currently not predicted from genome annotations. Expected outcomes of the project include the delineation of new metabolic processes that are common to all eukaryotes, the characterization of new enzymes families, and the ....Characterization of the dark metabolome of eukaryotic cells. The project aims to investigate the full metabolic potential of a group of eukaryotic organisms using advanced analytical and computational techniques. It will identify novel metabolites and enzyme activities that are currently not predicted from genome annotations. Expected outcomes of the project include the delineation of new metabolic processes that are common to all eukaryotes, the characterization of new enzymes families, and the generation of comprehensive metabolic databases. An improved understanding of cellular metabolism will provide direct benefits in biotechnology, food production, environmental monitoring and the diagnosis and treatment of human metabolic and infectious diseases. Read moreRead less