Functional Analysis Of The Notch Signalling Pathway In The Differentiation And Maintenance Of Pituitary Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,320.00
Summary
Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow ....Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone secreting cells to arise. Changes in these pituitary formation genes results in underdevelopment of the pituitary in newborn babies. In severe cases, where the pituitary has failed to form completely (panhypopituitarism), these babies are extremely ill and in some instances do not survive. We are studying the genes that belong to the Notch signalling pathway. These genes are important regulators of cell differentiation during the development of the brain, skin, bone and many other tissues. However, the role of the Notch signalling genes in pituitary development is not known. We have shown for the first time that these genes are active during pituitary development. To test the function of these genes in the pituitary, we will generate mouse models that either lack or inappropriately activate these genes. Our results will provide insight into the role of Notch Signalling genes in pituitary development in mice and humans. In this project, we also hope to identify cells in the pituitary that are able to give rise to multiple hormone secreting cell types. These stem cells are of significant clinical importance as they provide an avenue for the development of novel therapies for pituitary disorders in humans, based on the replacement of defective pituitary tissue with functional stem cell derived tissue.Read moreRead less
The Role Of Patched/Hedgehog Signalling In Common Human Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Mutations in the patched -hedgehog pathway are responsible for most of the common skin cancer basal cell carcinoma and some of the brain tumour medulloblastoma. Despite this knowledge we still do not know which cell in the skin gives rise to the basal cell carcinoma, and which cell in the brain gives rise to medulloblastoma. This application describes an approach using animal models to answer these questions and therefore further our understanding of how a normal cell becomes a tumour cell. In a ....Mutations in the patched -hedgehog pathway are responsible for most of the common skin cancer basal cell carcinoma and some of the brain tumour medulloblastoma. Despite this knowledge we still do not know which cell in the skin gives rise to the basal cell carcinoma, and which cell in the brain gives rise to medulloblastoma. This application describes an approach using animal models to answer these questions and therefore further our understanding of how a normal cell becomes a tumour cell. In addition this proposal extends out current studies to examine new gene family members in large tumour collections.Read moreRead less
Molecular and genetic analysis of epigenetic components in a model plant. Australia is a major exporter of agricultural food crops thus producers must maintain their competitive advantage in order to compete on the world stage. Food crops unfortunately have large, complex genomes that are not sequenced and a generation time of months that makes research outcomes slow to achieve. This project proposes to utilise a model plant that has a small completely sequenced genome and a short generation tim ....Molecular and genetic analysis of epigenetic components in a model plant. Australia is a major exporter of agricultural food crops thus producers must maintain their competitive advantage in order to compete on the world stage. Food crops unfortunately have large, complex genomes that are not sequenced and a generation time of months that makes research outcomes slow to achieve. This project proposes to utilise a model plant that has a small completely sequenced genome and a short generation time making it ideal to study the fundamental biological process of RNA silencing. Discoveries and outcomes from this project may have the potential to benefit Australian crops, ecosystems and human health.Read moreRead less
Early animal evolution: reconstructing the last common metazoan ancestor through the analysis of developmental and structural genes in sponges. All animals, from the simplest invertebrates to humans, arose from a common ancestor. Reconstruction of this ancestor requires the comparison of metazoan developmental genetic architectures. Here we contribute to this pursuit by studying a phylogenetically and biological appropriate metazoan system - marine sponge embryos and larvae. Using high-throughp ....Early animal evolution: reconstructing the last common metazoan ancestor through the analysis of developmental and structural genes in sponges. All animals, from the simplest invertebrates to humans, arose from a common ancestor. Reconstruction of this ancestor requires the comparison of metazoan developmental genetic architectures. Here we contribute to this pursuit by studying a phylogenetically and biological appropriate metazoan system - marine sponge embryos and larvae. Using high-throughput gene profiling techniques, we will analyse the developmental genetics underlying the sponge body plan. Commonalities shared between sponges and more sophisticated animals are likely to have been present in the "genetic toolkit" of the most ancient metazoan ancestor and, as such, is the genetic foundation from which all animal biodiversity arose.Read moreRead less
Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of th ....Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of the establishment of epigenetic state, combined with its heritability during mitosis, provides all the essential components for developmental noise. If our hypothesis proves correct, our work will have a major impact on the understanding of one of the most basic concepts in genetics.Read moreRead less