Patched Gene Family Control Of Epidermal Development And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
The skin is the largest organ in the body and functions as a barrier against infection and dehydration. From a clinical perspective we need to know how to regenerate skin for better wound healing and the treatment of burns. We have identified a genetic pathway that regulates the stem cells of the skin and this research will show us the mechanism whereby the skin develops and regenerates, as well as the possible manipulations we can use to increase healing in the clinic.
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
A knockout approach to identifying genes involved in epidermal development and homeostasis. These studies will identify new genes which play a role in the development or maintenance of the skin, some of which may subsequently be shown to play a role in disease. The project capitalises on an investment of tens of millions of dollars by the Wellcome Trust in generating a significant cohort of knockout mice. Our involvement in this international initiative will ensure Australia's participation in ....A knockout approach to identifying genes involved in epidermal development and homeostasis. These studies will identify new genes which play a role in the development or maintenance of the skin, some of which may subsequently be shown to play a role in disease. The project capitalises on an investment of tens of millions of dollars by the Wellcome Trust in generating a significant cohort of knockout mice. Our involvement in this international initiative will ensure Australia's participation in a project at the forefront of mouse genetics, using cutting edge infrastructure and technologies to provide insights into the complement of genes involved in skin biology. Models of interest will be repatriated to Australia for further study capitalising on existing infrastructure provided through the NCRIS funding program. Read moreRead less
Identification Of Genes Important In Myeloid And Haemopoietic Development By Genetic Screening In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
Zebrafish have emerged as a powerful experimental model in developmental genetics. Their favourable attributes include their reproductive biology, the optical clarity of embryos, and the accessibility of embryos for experimental procedures. Previous studies overseas have recovered over 1500 strains of zebrafish with inherited diseases due to induced mutations in about 500 genes. Many of these zebrafish have abnormalities of unexpected precision and are leading to new genes with novel specialized ....Zebrafish have emerged as a powerful experimental model in developmental genetics. Their favourable attributes include their reproductive biology, the optical clarity of embryos, and the accessibility of embryos for experimental procedures. Previous studies overseas have recovered over 1500 strains of zebrafish with inherited diseases due to induced mutations in about 500 genes. Many of these zebrafish have abnormalities of unexpected precision and are leading to new genes with novel specialized functions. About 50 mutant zebrafish strains exist in which red blood cell development is perturbed - this was easily recognized because the transparency of embryos enabled lack of blood be easily seen. Our new studies aim primarily to recover mutant zebrafish with disorders of white blood cell formation. We have identified methods to recognize failure of white blood cell formation in zebrafish, and will employ these methods to look for inherited disorders that specifically affect white blood cell development in a process called genetic screening. Fish with different sets of randomly mutated genes will be systematically screened to identify those with abnormal white blood cell development. We have tested our approach and identified several mutants affecting white blood cell development. Once these new strains of fish are identified, we will find the genetic lesion responsible for the abnormality in several of the most interesting strains by gene mapping and positional cloning. Hence, the mutant zebrafish identified in the screen will eventually lead to the discovery of new genes important in white blood cell growth and development. The fish themselves will provide insights into the causes of congenital diseases of white blood cells. Since many genes involved in early development are also important in cancer, we believe that newly identified genes will also help understand the causes of abnormal growth of white blood cells in leukaemia.Read moreRead less
The Role Of Non-coding RNAs In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
We have discovered a new mechanism by which genome activity is regulated. This project will test the hypothesis that this mechanism is critical for cell growth and embryonic development. It has the potential to identify new causes of birth defects and may also be relevant to understanding the etiology of other diseases such as cancer, resulting in improvements in diagnosis and management of disorders that present a major health care burden.
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise ....Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise novel inhibitors of caspases. Such inhibitors may in time be used as targets for development of therapeutic or diagnostic reagents aimed at manipulating the apoptotic process to diagnose, prevent or treat disease.Read moreRead less
Using integrated frontier and smart technologies to identify new drug targets for parasites causing major diseases in humans and animals. The national/community benefits are (1) enhanced focus on animal and human health biotechnology through the development of anti-parasite compounds and/or vaccines; (2) improved and sustainable control of important parasites with decreased risk of induction of drug resistance; (3) increased profitability of agricultural animal production; (4) consolidation of a ....Using integrated frontier and smart technologies to identify new drug targets for parasites causing major diseases in humans and animals. The national/community benefits are (1) enhanced focus on animal and human health biotechnology through the development of anti-parasite compounds and/or vaccines; (2) improved and sustainable control of important parasites with decreased risk of induction of drug resistance; (3) increased profitability of agricultural animal production; (4) consolidation of a technology platform for further applications in genomics and post-genomics of pathogens of global significance and construction of a pipeline for the validation of drug targets; (5) capturing the benefits from fundamental research and strengthening links between fundamental and applied research; (6) increasing the quality and quantity of scientifically skilled people in biotechnology.Read moreRead less