Phylodynamics for Single Cell Genomics . This project generates the mathematical framework required to look at single cell data in developmental systems and tissues. All cells in a multi-cellular organism derive from a single ancestral cell, generally the fertilised egg cell. Phylodynamics provides a framework to analyse and model this data, by connecting the shared ancestry of cells in an organism to the cell population and tissue dynamics. By developing the mathematical and statistical foundat ....Phylodynamics for Single Cell Genomics . This project generates the mathematical framework required to look at single cell data in developmental systems and tissues. All cells in a multi-cellular organism derive from a single ancestral cell, generally the fertilised egg cell. Phylodynamics provides a framework to analyse and model this data, by connecting the shared ancestry of cells in an organism to the cell population and tissue dynamics. By developing the mathematical and statistical foundations for the analysis of single cell data in a phylodynamic framework we will establish a powerful new computational tools for the analysis of tissues and developmental processes. 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
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
High-resolution multiscale modelling of pandemics: COVID-19 and beyond. The project aims to develop high-resolution computational models for pandemic mitigation and control, focussing on the novel coronavirus and its emerging variants, and leveraging demographic, genomic and epidemiological data. It expects to rigorously compare multi-scale effects of complex vaccination and social distancing strategies and quantify optimal responses under the COVID-19 induced uncertainty. The intended outcomes ....High-resolution multiscale modelling of pandemics: COVID-19 and beyond. The project aims to develop high-resolution computational models for pandemic mitigation and control, focussing on the novel coronavirus and its emerging variants, and leveraging demographic, genomic and epidemiological data. It expects to rigorously compare multi-scale effects of complex vaccination and social distancing strategies and quantify optimal responses under the COVID-19 induced uncertainty. The intended outcomes include computational models of how the most infectious viral variants emerge and spread in presence of interventions, how to predict the outbreaks, and which are the most vulnerable communities. This should make a significant economic and social impact, improving population health while maintaining a resilient economy.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
Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.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
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