Tissue Dynamics and Regeneration

Tissue Dynamics and Regeneration

Our group will move to the Max Planck Institute for Biophysical Chemistry in April 2020. 

Many animals have the intriguing ability to re-grow lost body parts, with starfish arm regeneration, salamander limb regeneration, or the regeneration of entire flatworms from tiny tissue pieces as just some 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 within a couple of days, even though the organ outwardly appears to be unchanging.

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 cues from other cells.  

How such dynamic assemblies of cells can reproducibly organize into organs and organisms raises many fundamental and unsolved questions. What defines shape, size, and proportions?  During regeneration, how can the remaining cells and tissues ‘know’ what and how much is missing? Or what limits the lifetime of individual cells versus the lifetime of the whole organism?

Flatforms are master of regeneration

We use planarian flatworms as model system to study these problems. As implied by the name, planarians are a type of worm with flattened body architecture. They occur worldwide in ponds, streams, on land, or even in the sea. A first intriguing aspect of their biology is an abundance of pluripotent adult stem cells. The rate of their 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 and growth. 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, a >800-fold range in cell numbers or close to a 10,000 fold range in weight. In some species, these fluctuations continue indefinitely, while other species age and die. And as if this were not feat enough, some planarians can literally be chopped into tiny pieces as small as 5,000 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, which we pursue in a highly interdisciplinary manner. We probe the molecular coordinate system that patterns planarian anatomy with biochemistry and cell biology. We sequence genomes and employ functional genomics in order to understand how patterning signals program stem cell fate choices or self-organize themselves into spatial patterns. We explore the quantitative basis of pattern formation, scaling, and size specification in close collaborations with physicists and theoreticians. And we undertake worldwide field sampling expeditions to collect ‘wild’ planarian species.

As a result, we maintain a large zoo of planarian species in the department that collectively represents a wide range of regenerative abilities, body sizes and shapes, cell turnover rates, organismal life spans, or reproductive strategies. In synergy between taxonomy and quantitative biology, we aim to understand the underlying molecular mechanisms and how they change in evolution. And to ultimately provide insights into such intriguing problems as the molecular specification of shape and size. Or why some animals regenerate, while others cannot? Or why some appear to live forever, while others age and die…?

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