Tissue Dynamics and Regeneration
Many animals have the intriguing ability to re-grow lost body parts, with salamander limb regeneration or the regeneration of entire flatworms from tiny tissue pieces as just two examples. In contrast, we humans and many other animals cannot regenerate missing arms or legs. But our livers still grow back to their original mass after surgery or the cells that make up our intestine undergo complete replacement every couple of days. All the above phenomena ultimately result from dynamic interactions amongst cells, the fundamental building blocks of organisms. But unlike the cinder bricks that make up a house, cells themselves are living entities that are born and that die, that move or change form and function. And cells continuously communicate, both influencing the functions of other cells whilst also responding to the influence of other cells. How such highly dynamic assemblies of cells can reproducibly organize into organs and organisms raises many fundamental and unsolved questions. What defines shape, size and proportions? What are the principles that govern cooperation and conflict within the dynamic cell societies that constitute individual organisms? What limits the lifetime of individual cells versus the lifetime of the whole organism? Or during regeneration, how can the remaining cells and tissues “know” what and how much is missing?
Flatworms are master of regeneration
We use planarian flatworms as model system. Planarians are a group of worms with flattened body architecture that occurs worldwide in ponds, streams, on land and in the sea. A first intriguing aspect of flatworm biology is an abundance of pluripotent adult stem cells, so called neoblasts. The rate of neoblast divisions is balanced with the death of differentiated cells, such that the entire animal continuously rebuilds itself. Feeding elicits a brief increase in the stem cell division rate that results in a net addition of new cells to the animal and a brief growth burst. Starvation shifts the balance towards the net loss of cells, causing the worms to literally shrink in size. Planarians, therefore, do not have a fixed body size and their external and internal body proportions fluctuate over a > 40-fold range in body length, >800-fold range in cell numbers or close to 10 000 fold range in weight. In some species, these fluctuations continue apparently indefinitely, while other species age and die. And as if this weren’t feat enough, some planarians can be chopped into tiny pieces as small as 5000 cells, yet manage to regenerate complete and perfectly proportioned worms from each and every piece.
Insights into how regeneration is regulated on the molecular level
The unique biology of planarians promises unique insights into fundamental problems of tissue dynamics and regeneration. With the fascinating regeneration of a tiny tissue piece back into a complete animal as a guiding challenge, the department employs a highly interdisciplinary compendium of methods and approaches. We probe molecular mechanisms with cell biology and biochemistry. We use genome sequencing and functional genomics approaches to explore the genetic basis of mechanisms and phenotypes. We employ theory and modeling to obtain insights into emergent system properties. And we embark on worldwide field sampling expeditions to collect “wild” planarian species and describe new species. As a result, we maintain a large zoo of planarian species as a rich resource for the comparative analysis of phenotypes.
Please see below for a detailed description of the major research directions within the department and the questions that intrigue us.