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.
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
Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.
How Do Cross-reactive Memory B Cells Affect Influenza Vaccine Titers?
Funder
National Health and Medical Research Council
Funding Amount
$798,049.00
Summary
Influenza vaccines are updated frequently to protect against the highly variable influenza virus. Despite careful selection of vaccine viruses, most influenza vaccines provide only modest protection and protection is poor some years. In turn, the response to vaccination varies between individuals. This probably reflects complex and variable histories of influenza infection and vaccination. The project investigates how past influenza exposure influences vaccine responses and effectiveness.
Regulation of histone methylation by polycomb-like proteins. This project aims to investigate how polycomb-like proteins regulate polycomb group (PcG) proteins and recruit them to their target genes. During the development of all multicellular organisms, PcG proteins are essential for keeping thousands of genes in a repressed state. PcG proteins are recruited to their target genes with the aid of their Polycomb-like protein cofactors, in a process that is poorly understood mechanistically. This ....Regulation of histone methylation by polycomb-like proteins. This project aims to investigate how polycomb-like proteins regulate polycomb group (PcG) proteins and recruit them to their target genes. During the development of all multicellular organisms, PcG proteins are essential for keeping thousands of genes in a repressed state. PcG proteins are recruited to their target genes with the aid of their Polycomb-like protein cofactors, in a process that is poorly understood mechanistically. This project will determine the mechanism that underpins the recruitment and regulation of PcG proteins by polycomb-like proteins. Outcomes will have relevance for most development processes of multicellular organisms.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100219
Funder
Australian Research Council
Funding Amount
$343,551.00
Summary
Molecular mechanism for the regulation of Polycomb repressive complex 2. This project aims to determine how the histone methyltransferase Polycomb repressive complex 2 (PRC2) is regulated. The project expects to generate new knowledge in transcription regulation and epigenetics. The intended outcome is to enhance the national capabilities in two important fields, Polycomb biology and cryo-electron microscopy (cryo-EM). This should provide significant benefits, including strengthening of the epig ....Molecular mechanism for the regulation of Polycomb repressive complex 2. This project aims to determine how the histone methyltransferase Polycomb repressive complex 2 (PRC2) is regulated. The project expects to generate new knowledge in transcription regulation and epigenetics. The intended outcome is to enhance the national capabilities in two important fields, Polycomb biology and cryo-electron microscopy (cryo-EM). This should provide significant benefits, including strengthening of the epigenetic community through the development of innovative research program in Polycomb biology and the establishment of a national world-class cryo-EM community.Read moreRead less
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
Molecular mechanism of the PRC-dependent RNA degradation by the rixosome. Polycomb repressive complexes (PRCs) and the rixosome are evolutionarily conserved enzymes that are required for silencing the developmental genes of multicellular organisms. This project aims to investigate how these key regulators maintain gene repression using cutting-edge approaches ranging from biochemistry, structural biology, cell biology to genomics. The expected outcomes include generating new knowledge in gene re ....Molecular mechanism of the PRC-dependent RNA degradation by the rixosome. Polycomb repressive complexes (PRCs) and the rixosome are evolutionarily conserved enzymes that are required for silencing the developmental genes of multicellular organisms. This project aims to investigate how these key regulators maintain gene repression using cutting-edge approaches ranging from biochemistry, structural biology, cell biology to genomics. The expected outcomes include generating new knowledge in gene regulation, strengthening the research capabilities of Australia in fundamental biology, and training the next generation of scientists. 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