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

整个生物医学研究的基础是在简单的模型生物体中进行的关键的详细实验。这些动物提供了相对便宜和快速的系统，在其中进行新发现，几乎所有基本的细胞和分子生物医学过程都首次在果蝇黑腹果蝇或线虫秀丽线虫中进行了基因描述。这是因为所有后生动物都分享了它们最后一个共同祖先身上存在的保守的进化特征。这两种模式生物之所以得到如此广泛的应用，是因为从历史上看，它们都可以进行遗传分析。在过去的二十年里，大量研究基因如何起作用的新方法被发明出来，这样就有可能对许多其他动物进行非常详细的研究。由于这些动物都是独立进化的，它们有可能拥有与我们自己的生物学相似的特征，而现有的模型则没有。例如，与哺乳动物不同，果蝇和线虫在其生活史上都不会广泛使用成体干细胞。在这里，我们建议使用蓝藻，这是另一种简单的动物，它确实使用成年干细胞作为其生活史的一部分。这些动物可以使用它们的干细胞来再生它们的整个身体，包括大脑。这是因为它们的成体干细胞能够几乎无限期地分裂并制造新组织，我们已经证明，控制脊椎动物干细胞的一些基因可能在人类身上具有保守的功能。这些基因中的许多可能在人类疾病中发挥作用，当它们突变为过度或不活跃时，我们想找到这些基因并描述它们在控制干细胞生物学中的功能，因为这可能对它们在人类中的作用以及它们如何参与疾病过程非常有用，特别是那些源自哺乳动物中流氓成年干细胞形成肿瘤的癌症。为了实现这一点，我们设计了一种敏感而快速的方法来研究新基因在成年干细胞及其环境中的功能，因为这两种基因都可能对了解干细胞的行为非常重要，这种行为错误可能会导致人类疾病，特别是癌症。

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.