From Endoderm To Gut: Regulation Of Lineage Allocation And Morphogenesis In The Murine Embryo
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
One of the most critical steps in early development is the generation of the full complement of cell types required to build the embryo. A thorough understanding of the mechanisms underlying this is vital for the development of methods for directing the differentiation of stem cells for use in regenerative medicine. The objective of our research is to understand the cellular and molecular mechanisms underlying the assignment of cells to particular fates and the establishment of the body plan of ....One of the most critical steps in early development is the generation of the full complement of cell types required to build the embryo. A thorough understanding of the mechanisms underlying this is vital for the development of methods for directing the differentiation of stem cells for use in regenerative medicine. The objective of our research is to understand the cellular and molecular mechanisms underlying the assignment of cells to particular fates and the establishment of the body plan of the embryo. The endodermal cell layer forms the lining of the embryonic gut which gives rise to the entire gastrointestinal tract, the respiratory tract and other structures including the liver and the pancreas during organogenesis. This investigation focuses on the questions of how the pluripotent progenitor cells are allocated to the endodermal lineage and how the embryonic gut is patterned during early development of the mouse embryo. Analysis of endoderm development will provide insights into the roles of the allocation of progenitor cells to tissue lineages, cell movement, and diversification and maturation of functional cell types. These processes are universally relevant to the formation of all types of organ primordia in the embryo. Understanding the complexity of tissue interactions and the interplay of molecular mechanisms of cell lineage choice and differentiation in the embryo is a major challenge. However, knowledge of the processes that drive tissue differentiation in the embryo is absolutely crucial for enhancing our ability to direct cell and tissue differentiation for the realization of cell-based technologies in biomedicine.Read moreRead less
One of the most critical steps in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. In the development of the head, this form-shaping process undertaken by different cell populations is coordinated by genetic activity that is triggered by signals received by cells. The objective of our research is to understand how one of the many signalling mechanisms, WNT signalling, works in making the ....One of the most critical steps in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. In the development of the head, this form-shaping process undertaken by different cell populations is coordinated by genetic activity that is triggered by signals received by cells. The objective of our research is to understand how one of the many signalling mechanisms, WNT signalling, works in making the head and face of the embryo. We will study the development of embryos of mice in which mutations have been introduced experimentally in genes that code for factors of the WNT signalling pathway. Understanding the complexity of tissue interactions and the interplay of molecular mechanisms of head formation in the embryo is a major challenge. However, knowledge of the processes in animal models will contribute to a better delineation of the role of signalling in normal head development. It will also help to direct the focus of future clinical investigations to the most relevant genetic determinants of birth defects of the head and face, which is present in about 8 per 10,000 births in Australia.Read moreRead less
The Contribution Of Gp130-Stat3 During Wnt-beta-catenin Induced Intestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,275.00
Summary
There is growing evidence that cancer is initiated and develops not by the deregulation of a single gene or signaling pathway, but by multiple events. We will study the co-operation between two pathways - gp130-Stat and Wnt. These signaling pathways are frequently deregulated in many types of cancer, however their interaction remains poorly understood. We shall explore their mechanism of interaction during intestinal cancer in order to develop a novel therapeutic target for this disease.
Investigating The Role Of The Notch4 Receptor In Blood Vessel Formation And Remodelling In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$653,086.00
Summary
We aim to understand how blood vessels form. This process is crucial for foetal development, and for injury repair in adults. When there is too much or too little blood vessel formation, diseases such as arthritis, blindness and osteoporosis can result. Also many tumours grow and spread by growing new blood vessels. We will study a signal that occurs between cells (Notch signalling) that is important in controlling the amount of blood vessel formation, by analysing in detail one component (Notch ....We aim to understand how blood vessels form. This process is crucial for foetal development, and for injury repair in adults. When there is too much or too little blood vessel formation, diseases such as arthritis, blindness and osteoporosis can result. Also many tumours grow and spread by growing new blood vessels. We will study a signal that occurs between cells (Notch signalling) that is important in controlling the amount of blood vessel formation, by analysing in detail one component (Notch4)Read moreRead less
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 Intersection Between Hedgehog And Notch Signalling In Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
Brain tumours are the second most common malignancy of childhood and the leading cause of cancer related death and disability in children. Medulloblastoma is the most frequent malignant childhood brain tumour, arising in the cerebellum. This application looks at the relationship between two genetic pathways responsible for medulloblastoma which are also drug targets. Understanding this interaction will lead to better treatment options for the disease.
Some bacteria can cause inflammation of the brain (bacterial meningitis). This leads to 170,000 deaths annually in the world. Many patients who survive after antibiotic treatment have lifelong disabilities like deafness, and problems of memory and learning. We aim to show that a certain biochemical pathway in the brain contributes to death and disability, with a view to identifying new drug treatments that can be used alongside antibiotics to improve disease outcomes.