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.
Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to und ....Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to understanding how new mutations arise in sperm and potentially affect offspring phenotype, adaptation and evolution. As chemicals, drugs and diet can affect epigenetic function, our studies will also contribute to determining how epigenetic inheritance affects environmental, agricultural and healthcare outcomes.Read moreRead less
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
Development of molecular markers for resistance to blackleg disease (Leptosphaeria maculans) in canola. Canola (Brassica napus) is a valuable oil seed crop grown in many parts of the world and contributes annually $A450 million to the Australian economy. The overall aim of this project is to develop molecular markers for blackleg resistance using Australian germplasm along with evaluation in Australian disease nurseries which are regarded worlwide to develop the highest levels of disease pressu ....Development of molecular markers for resistance to blackleg disease (Leptosphaeria maculans) in canola. Canola (Brassica napus) is a valuable oil seed crop grown in many parts of the world and contributes annually $A450 million to the Australian economy. The overall aim of this project is to develop molecular markers for blackleg resistance using Australian germplasm along with evaluation in Australian disease nurseries which are regarded worlwide to develop the highest levels of disease pressure. Once molecular marker systems are developed and evaluated, they will be applied to facilitate the selection of Nugrain's (Industry Partner) canola breeding programs. Any molecular markers and QTL developed for Australian cultivars would find commercial application in breeding programmes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100085
Funder
Australian Research Council
Funding Amount
$414,864.00
Summary
Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is ach ....Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is achieved by examining the molecular pathways that are activated following genetic mutation. This project is expected to strengthen Australian reputation in evolutionary genetics, and in turn enhance our understanding of how organisms adapt to changing environments.Read moreRead less
Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study ....Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study is important to every biological process in plants and animals driven by a change in gene expression. Expected Outcomes: This study will increase our biological knowledge in transcription control. Benefit: The knowledge gained has future applications in genomics and broad implications for biotechnology and industry.Read moreRead less
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
Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A b ....Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A better understanding of gene regulation in malaria parasites will help us to better combat the tricks utilised by this and other organisms to elude our immune systems.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
Epigenetic regulation of centromere and telomere chromatin. Epigenetics is a system that turns genes on and off without sequence alterations in the DNA. This process works by attaching chemical tags, known as epigenetic marks, to DNA. Centromeres and telomeres are chromosomal DNA domains essential for faithful chromosome segregation and genome stability. Their function and structural integrity are tightly regulated by specific epigenetic marks. This project aims to assess the functions of key ep ....Epigenetic regulation of centromere and telomere chromatin. Epigenetics is a system that turns genes on and off without sequence alterations in the DNA. This process works by attaching chemical tags, known as epigenetic marks, to DNA. Centromeres and telomeres are chromosomal DNA domains essential for faithful chromosome segregation and genome stability. Their function and structural integrity are tightly regulated by specific epigenetic marks. This project aims to assess the functions of key epigenetic factors including chromatin remodelers, histone variants and non-coding RNA in controlling centromere and telomere activity. The data should describe novel pathways that maintain the identity, transcription silencing, DNA replication fidelity and structural stability at these domains.Read moreRead less