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
How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowl ....How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expressi ....Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expression of only the required subset of genes. This will revolutionise our understanding of the mechanisms of gene control thereby shaping the field in the future. Significantly, this will allow new ways to manipulate gene expression that will impact biotechnology by providing new efficient ways to produce proteins or RNA. Read moreRead less
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
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.Read moreRead less
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101669
Funder
Australian Research Council
Funding Amount
$430,485.00
Summary
Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes . This project aims to address the fundamental question of how genes are switched off by studying a group of molecular off-switches, the polycomb group proteins. The project is expected to generate new knowledge in the area of gene regulation and epigenetics by combining innovative methods of structural biology and cell biology in an interdisciplinary way. The expected outcomes include a more complete picture of the molecu ....Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes . This project aims to address the fundamental question of how genes are switched off by studying a group of molecular off-switches, the polycomb group proteins. The project is expected to generate new knowledge in the area of gene regulation and epigenetics by combining innovative methods of structural biology and cell biology in an interdisciplinary way. The expected outcomes include a more complete picture of the molecular mechanisms that regulate gene expression and the development of novel methods to image the genome. This should provide significant benefits, such as facilitated development of gene editing tools and regulatory circuits for synthetic biology, as well as novel capabilities to image the genome at high resolution 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
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
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