Rerunning the evolution of an ancient bacterial propeller. This project aims to measure how the propeller which drives bacterial swimming originated and then evolved. This project expects to generate new knowledge in molecular evolution using interdisciplinary techniques in synthetic biology and biophysics to resurrect ancient proteins and test how they can be directed to evolve in a contemporary host. Expected outcomes include the development of new types of flagellar motor for applied uses in ....Rerunning the evolution of an ancient bacterial propeller. This project aims to measure how the propeller which drives bacterial swimming originated and then evolved. This project expects to generate new knowledge in molecular evolution using interdisciplinary techniques in synthetic biology and biophysics to resurrect ancient proteins and test how they can be directed to evolve in a contemporary host. Expected outcomes include the development of new types of flagellar motor for applied uses in synbio and microfluidics, and new methods to resurrect ancient proteins and evolve their function for purpose. This should provide significant benefits by delivering a de novo molecular motor for custom applications and galvanise public interest in how this iconic molecular complex originated and evolved.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL230100030
Funder
Australian Research Council
Funding Amount
$3,320,000.00
Summary
A walk on the wild side: understanding disease resistance across plants. Plants are in constant battle with pests and pathogens. Wild species host genetic diversity, providing sources of disease resistance, while the narrow genetic base of crop varieties leads to an increasing reliance on the unsustainable application of chemical fungicides. Here I will apply the latest genomics approaches to characterise disease resistance gene diversity across the plant kingdom. Comparison of gene diversity wi ....A walk on the wild side: understanding disease resistance across plants. Plants are in constant battle with pests and pathogens. Wild species host genetic diversity, providing sources of disease resistance, while the narrow genetic base of crop varieties leads to an increasing reliance on the unsustainable application of chemical fungicides. Here I will apply the latest genomics approaches to characterise disease resistance gene diversity across the plant kingdom. Comparison of gene diversity within and between plant families will improve our understanding of resistance gene evolution in wild species and the impact of domestication and breeding on resistance gene diversity. Translation of this knowledge will support breeding for crop resilience, leading to durable resistance and more sustainable crop productionRead moreRead less
Development of genetic technology for rodent population suppression. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are urgently required to tackle this massive challenge. Newly proposed “gene drives”, which might rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. Through innovative application of cutting-edge genome editing approaches, this proposa ....Development of genetic technology for rodent population suppression. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are urgently required to tackle this massive challenge. Newly proposed “gene drives”, which might rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. Through innovative application of cutting-edge genome editing approaches, this proposal aims to develop gene drive technology in mice as a prototypical vertebrate pest species. We will also develop cutting-edge mathematical models of rodent gene drives to identify crucial parameters for efficacious employment and investigate potential for impact on non-target populations.Read moreRead less
Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signa ....Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signalling pathways involved in this novel phenomenon. This should provide significant benefits to our fundamental understanding of biological processes that protect human genomes and provide a valuable dataset for research on telomere biology, DNA repair, and genome stability.Read moreRead less
Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply ....Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply Sequential Monte Carlo to update phylogenetic analyses continuously as new data arrives. Expected outcomes include new knowledge of statistical algorithms for evolutionary analysis, relevant to biological disciplines beyond infectious disease; and enhanced capacity for infectious disease analysis. Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
How do stem cells get specified during embryonic muscle development? This project aims to investigate the mechanisms by which muscle stem cells first form in the embryo. This project expects to generate new knowledge on the mechanism that patterns cell types in the embryonic myotome. Expected outcomes of this project include uncovering the developmental mechanisms of cell type specification in the myotome with specific reference to the generation of stem cells. This should provide significant be ....How do stem cells get specified during embryonic muscle development? This project aims to investigate the mechanisms by which muscle stem cells first form in the embryo. This project expects to generate new knowledge on the mechanism that patterns cell types in the embryonic myotome. Expected outcomes of this project include uncovering the developmental mechanisms of cell type specification in the myotome with specific reference to the generation of stem cells. This should provide significant benefits as it will inform how long lived tissue resident stem cells can be made in the first instance, knowledge that is critical for making stem cells on demand outside the animal and manipulating stem cells in living tissue.Read moreRead less
The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehe ....The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene.Read moreRead less
Assembling the building blocks in the blueprint of the embryonic head. This project aims to profile and impute the genome activity and validate the cellular and molecular mechanism underpinning the generation, in time and space, of diverse types of tissues that constitute the building blocks of the embryonic head. The knowledge gain enriches our understanding of the early steps of head formation during embryogenesis in the context of the niche conditions associated with the acquisition of progen ....Assembling the building blocks in the blueprint of the embryonic head. This project aims to profile and impute the genome activity and validate the cellular and molecular mechanism underpinning the generation, in time and space, of diverse types of tissues that constitute the building blocks of the embryonic head. The knowledge gain enriches our understanding of the early steps of head formation during embryogenesis in the context of the niche conditions associated with the acquisition of progenitor state, enhancement of lineage propensity, and driving early lineage differentiation. Expected outcome of this research on the developmental biology of a model organism provides a framework of the mechanism of establishing a blueprint of development that may be conserved across multiple mammalian species.Read moreRead less
Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover th ....Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover the molecular, genomic, and proteomic regulators or telomere privilege; determine the breath of telomere privilege in stem cell lineages; elucidate the functional significance of telomere privilege; and exploit telomere privilege to study fundamental biology related to telomeres and the DNA damage response.Read moreRead less