Functional Characterization Of The Regulatory Architecture Of Melanoma-associated Loci
Funder
National Health and Medical Research Council
Funding Amount
$645,663.00
Summary
Melanoma accounts for more than 75% of skin cancer related deaths. In Australia, >10,000 new cases are diagnosed yearly. In this proposal, we will apply novel genetic sequencing technologies developed in our laboratory to examine genomic regions that are associated with melanoma development. By focusing on selected areas, we will obtain a much deeper understanding of how these genes are regulated and find new ways of detecting and treating this disease.
Importance Of Histone Variant H2AZ Acetylation In Gene Activation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$611,737.00
Summary
DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel canc ....DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel cancer therapeutic target.Read moreRead less
H2A.Z Acetylation: Deregulation Of Enhancer Activity And 3D Chromatin In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$859,350.00
Summary
DNA is not linear but packaged in the cell nucleus in a three-dimensional (3D) structure in such a way that distal regulatory regions can interact to control gene expression. Our new data suggests that a chemical modification of the histone variant H2A.Z plays a critical role in the formation of the 3D chromatin structure. This project is aimed to dissect the role of H2A.Z in prescribing 3D structure, which will provide a more precise understanding of gene deregulation in cancer.
Understanding The Regulation Of The Location Of Chromosomes Within The Nucleus
Funder
National Health and Medical Research Council
Funding Amount
$333,612.00
Summary
The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regio ....The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regions of the genome attach to the nuclear lamina.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
Transcription At The Centromere: Roles In Formation, Maintenance And Function
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Every human has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome which governs the process of cell division and separation of replicated chromosomes. Defects in centromere function cause abnormalities in cell division that in turn cause a variety of genetic diseases including cancer. We propose to investigate the role that transcription at the centromere plays in determining correct centromere function.
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
Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways m ....Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways may lead to a novel methodology to activate silenced genes as well as determine the role of ncRNAs in genome evolution.Read moreRead less
Epigenetic inheritance: how does it work? This project aims to determine the mechanisms responsible for the inheritance of acquired traits. Sometimes the environment can have effects on the phenotype of not only the exposed individual, but also their children and grandchildren. While it is clear that this can occur, what is not clear is the mechanism by which this happens and the frequency at which it happens. This project will use the model organism Caenorhabditis elegans, innovative new techni ....Epigenetic inheritance: how does it work? This project aims to determine the mechanisms responsible for the inheritance of acquired traits. Sometimes the environment can have effects on the phenotype of not only the exposed individual, but also their children and grandchildren. While it is clear that this can occur, what is not clear is the mechanism by which this happens and the frequency at which it happens. This project will use the model organism Caenorhabditis elegans, innovative new techniques for the discovery of low abundance RNA molecules, and fluorescence microscopy to analyse structures within the cell nucleus to determine what the molecular mechanism is by which this "transgenerational epigenetic inheritance" occurs. This will have an impact on evolutionary theory, as well as long-term consequences for the understanding of human health and disease, and the impact of a changing climate on agriculture.Read moreRead less