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
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
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
Lifespan-dependent molecular shaping of the T cell receptor repertoire. Mammals have an intricate and highly complex immune system, whose function alters throughout life. Why and how this occurs is very unclear however, yet remains a crucial question. This project aims to provide fundamental knowledge on how the human lifespan shapes specific T cell receptors and determine molecular mechanisms underlying gain-of-function and loss-of-function during immunologically distinct phases of life. This p ....Lifespan-dependent molecular shaping of the T cell receptor repertoire. Mammals have an intricate and highly complex immune system, whose function alters throughout life. Why and how this occurs is very unclear however, yet remains a crucial question. This project aims to provide fundamental knowledge on how the human lifespan shapes specific T cell receptors and determine molecular mechanisms underlying gain-of-function and loss-of-function during immunologically distinct phases of life. This project will provide analysis of multi-dimensional, high throughput datasets to identify fundamental links between the transcriptional landscape and TCR signatures across human lifespan, thus will significantly answer key immunological questions in the field.Read moreRead less
Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance ....Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance that will foster establishment of new international linkages. This research will also identify strategies for engineering novel scaffolds that re-program cellular behaviour towards specific, applied outcomes, with potential benefit for the fields of synthetic biology, bioengineering and biotechnology.Read moreRead less