Discovering novel regulators of stem cell behaviour in a highly regenerative context

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The whole of biomedical research is underpinned by key detailed experiments performed in simple model organisms. These animals provide relatively cheap and rapid systems in which to make novel discoveries, with nearly all fundamental cell and molecular biomedical processes having their first genetic description in either the fruit fly Drosophila melanogaster or the nematode Caenorhabditis elegans. This is because all metazoan animals share conserved evolutionary features that were present in their last common ancestor. The reason that these two model organisms have been so extensively used is that historically they were amenable to genetic analysis. In the last twenty years a plethora of new ways of studying how genes work have been invented such that it is possible to study many other animals in great detail. As these animals have all evolved independently it is possible for them to have features in common with our own biology that the established models do not. For example, neither the fruit fly nor the nematode make extensive use of adult stem cells during their life history in contrast to mammals. Here we propose to use planarians, another simple animal that does use adult stem cells as part of its life history. These animals can use their stem cells to regenerate their whole body, including the brain. This is because their adult stem cells are able to divide and make new tissues almost indefinitely and we have already shown that some of the genes controlling planarian stem cells are likely to have conserved functions in humans. Many of these genes may have roles in human diseases when they are mutated to become over or under active We would like to find these genes and describe their functions in controlling stem cell biology as this is likely to be very informative about what they might do in humans and how they might be involved in disease proceeses, particularly those cancers that originate from from rogue adult stem cells in mammals form tumors.In order to achieve this we have designed a sensitive and rapid method forstudying the function of novel genes both in adult stem cells and in their environment, as both are likely to be important for understanding how stem cells behave and mistakes this behaviour can lead to human diseases, particularly cancer.