In Australia, chronic kidney disease costs >$1 billion per annum and can only be treated by dialysis or transplantation. Your kidney function depends upon what happened during your development as all the functional units of the kidney are made prior to birth from a stem cell population that then disappears. We have found a way to recreate these stem cells from adult cells. In this project, we will optimise this process and investigate whether regenerated stem cells can repair an adult kidney.
Aberrant Mesenchymal-epithelial Transition: A Pathogenic Mechanism In Tissue Maintenance And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$522,299.00
Summary
The causative genetic factors associated with aberrant changes of cellular properties are identified by analysing the profile and the control mechanism of gene expression. Specifically,this project will reveal how the transition of different patterns of tissue organization may be manifested in birth defects and malignant diseases.
Understanding The Kidney: From Morphogenesis To Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
In Australia, 11.3% of deaths are associated with chronic kidney disease with >$1 billion per annum spent on treating this condition. Kidney function throughout life depends upon what happened during your foetal development as all the functional units of the kidney are made prior to birth. In this project, we will use our understanding of normal kidney development to develop new regenerative approaches to the treatment of this condition.
Understanding The Regulation Of Kidney Morphogenesis In Order To Improve Renal Development
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be in ....Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be influenced.Read moreRead less
Developmental Genetics And Stem Cell Biology Of Birth Defects And Cell Based Therapy
Funder
National Health and Medical Research Council
Funding Amount
$823,008.00
Summary
Professor Tam is a mammalian embryologist studying the genetic and cellular mechanisms that form and shape the embryo and its organs during development. His work will help us to understand the causes of birth defects, how to prevent them and to correct the disorders by stem cell-based therapy.
Discovery And Analysis Of Vertebrate Intestinal Development Genes That May Play A Role In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,613.00
Summary
Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities ( ....Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.Read moreRead less
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
Globally, zebrafish are making a very significant impact on biomedical research. Zebrafish have a number of attributes that make them ideal models for the study of development and disease, including: - adults are relatively small, so housing is cheap - eggs are transparent, so early developmental processes can be visualized easily - development is rapid - organs are made in 1-7 days - zebrafish are vertebrates and thus have a gene complement very similar to humans - large numbers of eggs are pro ....Globally, zebrafish are making a very significant impact on biomedical research. Zebrafish have a number of attributes that make them ideal models for the study of development and disease, including: - adults are relatively small, so housing is cheap - eggs are transparent, so early developmental processes can be visualized easily - development is rapid - organs are made in 1-7 days - zebrafish are vertebrates and thus have a gene complement very similar to humans - large numbers of eggs are produced each week from a single mother, aiding experimentation - ENU mutagenesis screens have generated thousands of useful mutants, including an increasing number that accurately model human genetic diseases - high-resolution imaging of RNA and protein expression in whole embryos is easy - drugs and chemicals can be easily tested for activities in zebrafish by adding them to the water Becuase of these attributes, zebrafish are becoming the model organism of choice for the study to human development and disease - indeed, the zebrafish field is growing at three times the rate of the mouse field. The international biomedical community has invested very heavily in infrastructure to aid the zebrafish community in realising the potential of this model. In Australia we have very strong basic research teams whom have embraced zebrafish mdoels. However, we lag behind other parts of the world in that, as yet, we have not had much specific funding allocated to animal model infrastructure. This Enabling Grant will build unique infrastructure by bringing together the zebrafish community with two areas in which Australia is very strong - genomics and biodiversity. This will result in a greatly enhanced ability to determine how genes work, and a pipeline for screening Australia's rich source of natural products and chemical libraries for activites against common human diseases such as cancer, dementia, and muscle diseases using zebrafish models.Read moreRead less