The Role And Underlying Mechanisms Of Constitutional Epigenetic Silencing In Cancer Predisposition
Funder
National Health and Medical Research Council
Funding Amount
$218,617.00
Summary
Familial and young onset bowel and uterine cancer are usually caused by the inheritance of spelling mistakes in the genetic code within a set of cancer-protection genes. Recently, some patients were identified with their gene switched off by paralysing chemicals instead. This study aims to identify additional cancer cases with gene paralysis, determine if this arises in the presence or absence of a genetic change in front of the gene, and how gene paralysis is transmitted to the next generation.
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.
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most import ....Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most importantly, we will test our hypothesis that tumours all arose from a single ancestral cancer cell that is transmitted between animals. A cellular transmission has frightening implications for spread of disease, but will allow us to develop appropriate therapeutic strategies to save a unique Australian marsupial from extinction.Read moreRead less
Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of di ....Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of disease.Read moreRead less
Discovering sex determining genes in a reptile with genetic and environmental sex determination. Reptile sex determination is particularly fascinating because it is triggered either by genes on sex chromosomes or by the nest temperature. This project will identify and characterise candidate sex determining genes in a model reptile to understand how genes control sexual differentiation and how they interact with temperature.
Was an ancient bird-like sex chromosome system ancestral to reptiles and mammals? Recent discoveries reveal amazing similarity in the sex chromosomes of distantly related animals. This project will use advanced DNA technology to explore diverse sex chromosomes in reptiles to discover whether this signifies ancient and unsuspected common ancestry, or the convergent redeployment of genes and chromosomes predisposed to determine sex.
DNA methylation in insect social evolution. This project will investigate the evolutionary relationship between DNA methylation and the advanced sociality displayed by bees, ants and wasps. The project will map DNA methylation across the social insects and test whether it has coevolved with sociality. It will also determine how a vital social cue, the queen pheromone, influences the worker methylome. Finally, it will apply quantitative genetic and methylomic methods to wild insects, revealing pa ....DNA methylation in insect social evolution. This project will investigate the evolutionary relationship between DNA methylation and the advanced sociality displayed by bees, ants and wasps. The project will map DNA methylation across the social insects and test whether it has coevolved with sociality. It will also determine how a vital social cue, the queen pheromone, influences the worker methylome. Finally, it will apply quantitative genetic and methylomic methods to wild insects, revealing patterns of selection and inheritance in epigenetic and phenotypic traits. By combining genomic and evolutionary methods, the project will advance the ongoing debate about the importance of methylation to sociality and extreme phenotypic plasticity. It will contribute to a quantum leap in our understanding of DNA methylation and sociobiology and mark the first application of quantitative genetics to wild insects.Read moreRead less
Variation in the arginine vasopressin 1a receptor (AVPR1a) gene, the social environment, general health and wellbeing. The project aims to investigate how the arginine vasopressin 1a gene affects gene expression and influences social behaviour and ultimately health and wellbeing. This research will contribute to understanding the importance of individual differences in social policy and interventions aimed at improving health and wellbeing.