Investigating Widespread Regulation Of Gene Expression Through Intron Retention
Funder
National Health and Medical Research Council
Funding Amount
$363,026.00
Summary
We recently discovered a hidden type of gene regulation that appears to be altered in diverse cancers including leukaemia, melanoma and colon cancer. We will explore this widely relevant mechanism using molecular and computational tools. We created the only computer program able to detect this type of regulation and will now share our discovery with cancer scientists through cloud computing technology.
Computational Reconstruction And Validation Of A Gene Regulatory Network Controlling Differentiation Of B Cells To Antibody-secreting Plasma Cells
Funder
National Health and Medical Research Council
Funding Amount
$618,152.00
Summary
Regulation of B cell differentiation, which occurs when our body responds to antigen infection is tightly controlled by a gene regulatory network. This project will be the first study to reconstruct a regulatory network for this process by using genome-wide expression and transcription factor binding data. The research finding from this study will elucidate the molecular mechanisms regulating this process and will shed new light on how this network is altered in lymphoma and myeloma.
Unravelling Gene Networks In Heart Development And Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$397,724.00
Summary
One in 100 Australian babies are affected by heart malformations. The heart is a complex organ and its formation is likewise orchestrated by a complex network of genes. As our current knowledge of this network is limited, I aim to employ cutting-edge bioinformatics approaches to draw a comprehensive picture of genes required to build a healthy heart and to reveal which gene interactions are altered in congenital heart disease, thereby opening new perspectives for network biology-based therapies.
Interactions Between Aberrant Transcriptional Programs And Methylation In Primary Myelodysplasia And Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Impaired development of blood stem cells leads to haematological disease such as leukaemia. State of the art next-generation sequencing and bioinformatics identified molecular pathways essential for normal blood development and a core set of these genes repressed in leukaemia. Understanding the mechanism by which these genes are re-activated by the non-specific drug azacitidine contributes to the development of new therapeutics with increased efficiency and reduced side effects.
Improving Bioinformatic Methods For Studying Gene Regulation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
New methods for analysing genome-wide data will be developed to ease the data analysis bottleneck that currently exists in medical research. Modelling variation in gene expression from single cells, in screens designed to uncover gene function and assays that measure the factors that turn genes on or off will be the focus. Free software will be developed and made available to researchers worldwide to help them interpret the large and complex data sets that are now routine in genomic medicine.
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
Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pa ....Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pathogenic behaviour and biomass production.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