Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying ....Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying regulators of lipid metabolism. The large diversity in humans necessitate sufficient sample sizes to identify true genetic regulators, but to date techniques capturing phenotypic data (lipids) have been largely limited. It is anticipated that this study will identify new regulators of lipid metabolism in humans.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
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
Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new ....Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new knowledge about the unique biology of Australia's marsupial fauna.This project will provide significant benefits, including enhanced capacity for reproduction research in Australia, new international collaborations between Melbourne and Yale, and a new explanation for the puzzling role of inflammation in pregnancy.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
Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The pr ....Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The project will provide fundamental advances in our knowledge of the nutrient transport during pregnancy that is required to produce a healthy baby.Read moreRead less
Design of the cardiovascular system of living and fossil vertebrates. This project aims to understand how the heart and blood vessels evolved in mammals, birds, reptiles and fish to achieve efficiency. The heart is the most important organ for life. The project will study the structure and function of vertebrate animals’ hollow and spongy hearts to show how energetics shaped their evolution. It will measure arterial holes in bone to gauge brain and bone metabolism, which opens up a new way to me ....Design of the cardiovascular system of living and fossil vertebrates. This project aims to understand how the heart and blood vessels evolved in mammals, birds, reptiles and fish to achieve efficiency. The heart is the most important organ for life. The project will study the structure and function of vertebrate animals’ hollow and spongy hearts to show how energetics shaped their evolution. It will measure arterial holes in bone to gauge brain and bone metabolism, which opens up a new way to measure metabolism in extinct animals directly from fossils, rather than by inference from living relatives. The expected outcome is to correlate cardiovascular design and metabolic rates of organs.Read moreRead less