Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Beyond the genome: unravelling the intricacies of epigenetic regulation using the honey bee model. Epigenetic mechanisms, such as DNA methylation, provide the interface between genome and environment. Abnormalities in epigenetic regulation lead to cancer and other diseases. The project will be using the alternative phenotypes in honeybees, fertile queens and sterile workers, to understand how dietary factors control conditional gene expression by methylation
Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how tem ....Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how temperature reverses chromosomal sex determination in dragon lizards. This could show how climatic extremes affect the biology of climate sensitive reptiles, and understand their vulnerability to climate change.Read moreRead less
Do chromosomal rearrangements drive genomic evolution and speciation? This project aims to gain an understanding of the processes driving speciation using the internationally recognised and uniquely Australian rock-wallaby model system, where speciation appears to be caught in the act. Speciation is a fundamental evolutionary process, yet one that is not well understood. The project plans to use recent advances in marsupial genomics, bioinformatics, cytogenetics and epigenetics to determine the ....Do chromosomal rearrangements drive genomic evolution and speciation? This project aims to gain an understanding of the processes driving speciation using the internationally recognised and uniquely Australian rock-wallaby model system, where speciation appears to be caught in the act. Speciation is a fundamental evolutionary process, yet one that is not well understood. The project plans to use recent advances in marsupial genomics, bioinformatics, cytogenetics and epigenetics to determine the role that chromosome rearrangements play in the speciation process. This may provide critical knowledge for understanding the process of speciation and for future decisions regarding the effective management of biodiversity.Read moreRead less
The hunt for Ribonucleic Acid riboswitches and genetic sensors of metabolic flux in plants. Ribonucleic Acid (RNA) contains both structural and sequence information that coordinates feedback of metabolic processes in response to environmental change, thereby promoting cellular adaptation and survival. This project will discover ancient RNA modules and structural switches in plants that sense chemical reactions and regulate pathway flux.