Understanding the regulation of adult stem cell migration during regeneration.

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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.