Understanding the regulation of adult stem cell migration during regeneration.

在我们的一生中，我们体内的细胞通过分裂和移动来替换老化或受损的细胞，从而积极地维持我们的组织和器官。细胞可能会因正常的磨损、物理损伤(如割伤或烧伤)或各种疾病而受损。大多数这种修复和维护是由一组特殊的细胞进行的，这种细胞被称为“干细胞”，当需要时，它会在我们的身体中形成细胞类型。我们现在认为，许多衰老过程、许多发育障碍以及事实上许多癌症都是由干细胞出错引起的。干细胞DNA的损伤可能导致它们无法进一步分裂，以帮助维持我们的组织和器官，最终导致衰老，但更重要的是，这种损伤也可能导致干细胞行为的改变，使它们过度增殖和过度迁移，从而导致癌症。因此，了解干细胞是如何维持组织的，以及导致组织出错的因素是很重要的。在这个项目中，我们特别感兴趣的是干细胞如何正确地迁移到伤口部位，以及在这个过程中会出现什么问题。为了研究这一点，我们正在使用一种简单的动物模型系统，由于成体干细胞的数量，它能够产生令人惊叹的再生壮举，使其能够再生所有成体组织和器官，包括大脑。与更复杂动物的干细胞相比，这些动物体内的干细胞，即所谓的脊椎动物蠕虫，更容易获得和研究，而且更符合伦理道德。由于许多基因在进化过程中是保守的，我们所发现的与行星动物的合作将继续为我们自己的生物学提供有用的见解。例如，我们最近描述了与人类癌症直接相关的新基因和基因相互作用。我们还发现，在正常迁移过程中，迁移过程本身会对迁移干细胞的基因造成损害，因为细胞迁移的物理过程会对包含基因组的细胞核造成压力。随着细胞的迁移，这种损伤得到适当的修复是很重要的，我们的数据到目前为止表明，如果不进行修复，迁移就会停止。我们将使用最先进的分子方法来了解正常的干细胞迁移是如何在基因水平上受到控制的，以及当浮游生物的干细胞过度迁移形成肿瘤样突起时，这种正常控制会发生什么。我们还将研究细胞迁移和DNA修复之间的相互作用，因为这可能是干细胞以前未被认识到的潜在损伤的来源。OUT项目的发现将为与包括癌症在内的人类疾病相关的过程提供新的基本见解。

Throughout our lives the cells in our body actively maintain our tissues and organs by dividing and moving to replace aged or damaged cells. Cells can be damaged by normal wear and tear, by physical damage like a cut or a burn or because of various diseases. Much of this repair and maintenance is carried out by a special set of cells called "stem cells" that make the cell types in our bodies, as and when required. We now think that much of the aging process, many developmental disorders and in fact many cancers are caused by stem cells going wrong. Damage to the DNA of stem cells can lead to them being unable to divide further to help maintain our tissues and organs leading eventually to aging, but even more importantly this damage can also lead to changes in how stem cells behave so that they over proliferate and over migrate to cause cancer. So understanding how stem cells maintain tissues and the factors that can contribute to them going wrong is important. In this project we are specifically interested in how stem cells migrate correctly to the site of a wound and what can go wrong during this process. In order to study this we are using a simple animal model system that is capable of amazing regenerative feats because of a population of adult stem cells, that allow it to regenerate all adult tissues and organs, including the brain. These stem cells in these animals, called planarian worms, can be more easily and ethically accessed and studied than the stem cells of more complex animals. As many genes have been conserved over evolutionary time what we have discovered working with planarians continues to provide useful insights into our own biology. For example, we have recently described new genes and genetic interactions that are directly relevant to humans cancers. We have also found out that the process of migration can in itself cause damage to the genes of migrating stem cells during normal migration, as the physical progress of cell migration causes stress upon the nucleus that contains the genome. It is important that this damage is repaired properly as cells migrate, and our data so far indicate that without repair migration stops.We will use state-of-the-art molecular approaches to understand the how normal stem cell migration is controlled at the genetic level and what happens to this normal control when stem cells in planarians over-migrate to form tumor-like outgrowths.We will also investigate the interplay between cell migration and DNA repair, as this could be particularly important as a potential source of previously unappreciated source of damage to stem cells. The findings of out project will provide new fundamental insights into processes relevant to human diseases, including cancer.