Illuminating the microbial world using genome-based fluorescence microscopy. Our understanding of microbial diversity on Earth has been fundamentally changed by metagenomic characterisation of natural ecosystems. Traditional approaches for visualising microbial communities are time-consuming and provide limited information about the identity of specific microorganisms. The proposed research aims to combine single cell genomics and super resolution microscopy for novel, high-throughput, genome-b ....Illuminating the microbial world using genome-based fluorescence microscopy. Our understanding of microbial diversity on Earth has been fundamentally changed by metagenomic characterisation of natural ecosystems. Traditional approaches for visualising microbial communities are time-consuming and provide limited information about the identity of specific microorganisms. The proposed research aims to combine single cell genomics and super resolution microscopy for novel, high-throughput, genome-based techniques to visualise microorganisms, plasmids and viruses, with strain level specificity. The application of these highly scalable approaches will provide comprehensive and unprecedented insight into the fine-scale dynamics and evolution of environmentally and biotechnologically important microbial communities.Read moreRead less
A molecular/morphological view of animal evolution based on marsupials. This project aims to provide high-accuracy methods of evolutionary inference extendable to nearly all other organisms. It aims to research the evolution of animal diversity and calibrate evolutionary timescales on a case study of marsupial mammals, and differentiate between internal and external factors that govern animals’ ability to adapt and diversify. The project will collate a large, open-source three-dimensional catalo ....A molecular/morphological view of animal evolution based on marsupials. This project aims to provide high-accuracy methods of evolutionary inference extendable to nearly all other organisms. It aims to research the evolution of animal diversity and calibrate evolutionary timescales on a case study of marsupial mammals, and differentiate between internal and external factors that govern animals’ ability to adapt and diversify. The project will collate a large, open-source three-dimensional catalogue of the evolving marsupial skeleton, which could provide a detailed and publicly accessible narrative of the evolutionary past and future adaptability of Australian marsupials. The proposed development of methods to quantify the effect of past and present biodiversity crises (e.g. environmental change) is expected to inform longer-term conservation planning.Read moreRead less
Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play ....Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play a key role. It will also support the development of billion dollar industries focused on the use of beneficial microbes in agriculture, plant, animal, and human health.Read moreRead less
Evolution of the marsupial gut microbiome and adaptation to eucalypt toxins. Eucalyptus leaves comprise all or part of the diet of some marsupials including koalas. Gut microbiota assist in the ability of these folivores to tolerate eucalyptus toxins although present understanding of this process is rudimentary. This project aims to use culture-independent molecular methods to identify and characterise gut populations involved in phytochemical detoxification by comparative analysis with diprotod ....Evolution of the marsupial gut microbiome and adaptation to eucalypt toxins. Eucalyptus leaves comprise all or part of the diet of some marsupials including koalas. Gut microbiota assist in the ability of these folivores to tolerate eucalyptus toxins although present understanding of this process is rudimentary. This project aims to use culture-independent molecular methods to identify and characterise gut populations involved in phytochemical detoxification by comparative analysis with diprotodont relatives that are not capable of digesting eucalyptus leaves. This will highlight evolutionary convergence of gut microbiomes in toxic folivores and reveal mechanisms by which microorganisms respond to and metabolise eucalypt toxins. A broader evolutionary context of marsupial digestive function will assist in ongoing conservation efforts.Read moreRead less
Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400 million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what spe ....Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400 million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what specific changes led to the evolutionary success of a protein, and to re-run evolution to generate proteins that perform in conditions suitable for industrial and agricultural applications, in particular the production of hydroxylated fatty acids for bioplastics. By examining proteins from many life forms, the project plans to develop a novel bioinformatics strategy to understand their evolution and engineer new proteins for use in production of chemical commodities.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water ....Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water and soil should lead to deeper understanding of the dynamics, variation and transfer of genetic material within these resources’ microbial communities, strategies to manage microbial diversity, and improved productivity and long-term sustainability for these resources.Read moreRead less
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
Tracing nature's template: using statistical machine learning to evolve biocatalysts. In this project new computational methods will be developed to design nature-inspired, biological catalysts for industrial purposes. Such methods will enable catalysts to be designed that can improve the effectiveness and environmental footprint of drug development, agricultural and specialist chemical production and environmental remediation.