Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.
The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemi ....The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemical modifications impact cell specific gene nuclear positioning and how this regulates changes in gene expression associated with immune cell activation. An outcome will be identification of novel molecular mechanisms that will have broad applicability across cellular biology, and provide novel targets for drug development.Read moreRead less
Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for ....Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for important agronomic traits including disease resistance, flowering time and legume nitrogen fixation which will enable plant breeders to identify and apply novel genes and allelic variants for use in breeding programmes, accelerating the production of improved crop varieties.Read moreRead less
Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will gene ....Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will generate basic scientific knowledge and new intellectual property that will afford new opportunities for research and development. The outcomes of this project will help to devise strategies to treat diseases such as autoimmunity, cancer and metabolic syndrome, and will thus benefit veterinary and human health.Read moreRead less
RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with ....RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with mechanism and function determined by novel CRISPR editing of a transgenic mouse model. The significant benefit will be a more complete understanding of RNA mechanisms of immune response, which will be critical in informing future advances in the rapidly developing areas of RNA-based biotechnologies and synthetic immunology.Read moreRead less
Characterising structural variation in the canola genome. Characterising structural variation in the canola genome. This project aims to develop and apply genomic tools to identify and characterise structural genome variation in canola, a major Australian export crop, to better understand genome evolution and accelerate canola breeding. Advances in DNA sequencing revolutionise our understanding of crop genomes, their evolution and impact on the inheritance on agronomic traits. Variation of genom ....Characterising structural variation in the canola genome. Characterising structural variation in the canola genome. This project aims to develop and apply genomic tools to identify and characterise structural genome variation in canola, a major Australian export crop, to better understand genome evolution and accelerate canola breeding. Advances in DNA sequencing revolutionise our understanding of crop genomes, their evolution and impact on the inheritance on agronomic traits. Variation of genome structure between individuals could be important in the inheritance of important agronomic traits. Recent advances in technology permit the detailed characterisation of structural variation on a previously unfeasible scale. Anticipated outcomes are enhanced global food security, supporting rural Australian economies, and accelerating the improvement of other major crops.Read moreRead less
Complexities of the mitochondrial transcriptome. This project aims to understand mitochondrial gene expression and energy production. Energy production is important for living things to grow and develop. In mammals, the mitochondria, the energy producing “powerhouses of the cell”, contain their own genetic assembly instructions. This project aims to understand these genetic instructions, revealing how genes control energy production. This project will characterise the genetic instructions, the m ....Complexities of the mitochondrial transcriptome. This project aims to understand mitochondrial gene expression and energy production. Energy production is important for living things to grow and develop. In mammals, the mitochondria, the energy producing “powerhouses of the cell”, contain their own genetic assembly instructions. This project aims to understand these genetic instructions, revealing how genes control energy production. This project will characterise the genetic instructions, the mitochondrial transcriptome and the proteins that control them. These advances are expected to provide a mechanistic understanding of how gene expression responds to changes in cellular energy demands. This knowledge will generate new biotechnological tools for Australian science and will have important long-term implications for improving agriculture and medicineRead moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100398
Funder
Australian Research Council
Funding Amount
$448,365.00
Summary
The Life And Death Of Plant Genes. My recent work has demonstrated that in contrast to animal genes, many plant genes show presence/absence variation within a species, with associated trait variation. In this project, I will explore models of gene birth and death by comparing genomes of Brassicaceae, including the model Arabidopsis and Brassica crop species. By comparing many genomes I will learn how new genes were born. I will build models that predict the likelihood of gene loss based on a gen ....The Life And Death Of Plant Genes. My recent work has demonstrated that in contrast to animal genes, many plant genes show presence/absence variation within a species, with associated trait variation. In this project, I will explore models of gene birth and death by comparing genomes of Brassicaceae, including the model Arabidopsis and Brassica crop species. By comparing many genomes I will learn how new genes were born. I will build models that predict the likelihood of gene loss based on a gene’s physical environment, function, and expression. The project will build on our understanding of plant genetic diversity. Expected outcomes of this research include the identification of key genomic elements in gene birth and loss and support strategies to improve plant cultivars.Read moreRead less
Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across f ....Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across fly species and vertebrates, and their functional effect on testis morphogenesis and distortion of female/male sex-ratio. The project also studies splicing-dependent small RNAs and miRNA-target interaction. This research could have applications from animal development to human pathology.Read moreRead less
Radical change in the architecture of a nucleus: loss of typical DNA organisation systems in dinoflagellates. The genetic blueprint of all higher cells is stored in the cell nucleus, and proteins called histones provide the filing system for compactly stacking and organising the cell's DNA. One group of organisms, the dinoflagellate algae, have lost this histone system. This project will provide insight into their alternative DNA management systems.