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
Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integr ....Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integration of Huc, including the basis of its remarkably high affinity and oxygen insensitivity compared to previously studied hydrogenases. This project will enable biotechnological applications, as the first study of an enzyme that extracts energy from air, and has broad ecological and biogeochemical implications.Read moreRead less
Enhancing Genomic Prediction for Changing Environments in Wheat. Adverse weather is the primary risk faced by the Australian agriculture industry. This Project aims to develop the next generation of agriculture tools to unlock natural potential in wheat and improve yield stability across seasons and regions. Drawing on crop physiology, genetics and integrated modelling, this Project expects to generate new knowledge and technologies to untangle genetic and environmental interactions that affect ....Enhancing Genomic Prediction for Changing Environments in Wheat. Adverse weather is the primary risk faced by the Australian agriculture industry. This Project aims to develop the next generation of agriculture tools to unlock natural potential in wheat and improve yield stability across seasons and regions. Drawing on crop physiology, genetics and integrated modelling, this Project expects to generate new knowledge and technologies to untangle genetic and environmental interactions that affect productivity, enhance predictive capability, and initiate advanced breeding strategies to develop new crop varieties with superior resilience against changing climates. This should provide significant benefits, such as profit stability for wheat growers, elevated global market position and improved food security.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Living on air: how do bacteria scavenge atmospheric trace gases? This project aims to determine the molecular and cellular basis of atmospheric trace gas oxidation by bacteria. Bacteria have a remarkable ability to adapt to resource limitation and environmental change by entering dormant states. Our research has shown they survive in this state by using atmospheric hydrogen and carbon monoxide as energy sources. This interdisciplinary project will determine how bacteria achieve this by elucidati ....Living on air: how do bacteria scavenge atmospheric trace gases? This project aims to determine the molecular and cellular basis of atmospheric trace gas oxidation by bacteria. Bacteria have a remarkable ability to adapt to resource limitation and environmental change by entering dormant states. Our research has shown they survive in this state by using atmospheric hydrogen and carbon monoxide as energy sources. This interdisciplinary project will determine how bacteria achieve this by elucidating the regulation, mechanism, and integration of the three uncharacterised enzymes that mediate this process. Outcomes and benefits include understanding of the processes that facilitate bacterial persistence, regulate atmospheric composition, and in turn support resilience of natural ecosystems.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
Cell-Sort MultiTool: a Novel Platform for Bacterial Single-Cell Analysis . This project aims to advance molecular understanding of antibiotic resistance in bacterial populations at the single-cell level, using an innovative approach integrating microfluidics, microscopy and genomics. The study of individual bacterial cell genetics is essential to provide fundamental insights into heterogeneous resistance, an important component of resistance development. Expected outcomes include a new platform ....Cell-Sort MultiTool: a Novel Platform for Bacterial Single-Cell Analysis . This project aims to advance molecular understanding of antibiotic resistance in bacterial populations at the single-cell level, using an innovative approach integrating microfluidics, microscopy and genomics. The study of individual bacterial cell genetics is essential to provide fundamental insights into heterogeneous resistance, an important component of resistance development. Expected outcomes include a new platform technology for high-throughput multiplexed screening and improved knowledge of bacterial heterogeneity, informing antibiotic usage. This interdisciplinary project should yield significant benefits in society and economy by reducing healthcare costs, boosting health for Australians and commercialising advanced technologies. Read moreRead less
How does the noncoding genome regulate gene expression in the human brain? The non-coding genome is recognized as a major player in orchestrating gene expression in higher eukaryotes. This project aims to identify regions of the human genome that are important for gene expression during neuronal differentiation and depolarisation (i.e. neural enhancers), and to investigate their evolutionary properties. The roles of non-coding DNA in regulating the dynamic gene expression patterns underlying com ....How does the noncoding genome regulate gene expression in the human brain? The non-coding genome is recognized as a major player in orchestrating gene expression in higher eukaryotes. This project aims to identify regions of the human genome that are important for gene expression during neuronal differentiation and depolarisation (i.e. neural enhancers), and to investigate their evolutionary properties. The roles of non-coding DNA in regulating the dynamic gene expression patterns underlying complex human brain functions remains to be elucidated. By combining transcriptome quantification and bioinformatics methods, this project will close an important knowledge gap in our understanding of transcriptional regulation underlying human brain function. This will provide benefits such as the potential to influence public health policy including in cognitive functions and aging.Read moreRead less