Identification Of Genes Regulating Vertebrate Intestinal Development
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Colorectal cancer (CRC) causes 14 per cent of all cancer deaths in Australia. 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 (mutation ....Colorectal cancer (CRC) causes 14 per cent of all cancer deaths in Australia. 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 propose to identify a set of genes that control the development of the intestine in a small tropical fish, the zebrafish. Zebrafish are vertebrate organisms, closely related to mice and man. Essentially all the pathways regulating development are conserved in the three species. The zebrafish offers several advantages: they are small, easy to breed, cheap to maintain and, most importantly, their embryos are transparent, making it possible to visualise development in live embryos in a simple microscope. Our project will use a panel of mutant strains of zebrafish that have an array of visible abnormalities in intestinal development. The abnormalities were induced using a chemical that produces single base pair changes in DNA. An established technique called positional cloning will allow us to identify the genes in which the mutations have been introduced, and provide a genetic explanation for the intestinal abnormalities. Upon identification of the mutated genes, our ultimate aim will be to test whether they also play a role in the development of CRC, using mouse models and human tissues.Read moreRead less
A Fluorescent Zebrafish Model Of Endodermal Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The most catastrophic event in cancer progression is when individual cancer cells move to other areas of the body and develop into secondary tumours. This very complex process shows striking similarities to cell movements during embryogenesis. In this project, we use a model system, the zebrafish, to analyse how cells move during embryogenesis. We will determine the genes required for cell movements in the zebrafish embryo, so we can find the corresponding genes in human cancers.