Research

My lab is interested in cell motion and tissue formation during embryogenesis and regeneration. Cell and tissue dynamics constitute a beautiful problem of bridging scales: On the microscopic scale, cells are expressing particular genes which determine their identities and also their fate during morphogenesis. These molecular determinants then lead to the macroscopic phenomena of cell movements and tissue arrangements, for which one needs a continuum description in terms of active fluids. Taking into account that the number of cells is fairly small (10^3 − 10^4), a complete coarse graining is not possible, and a characterization of both mesoscopic (individual cell motion) and macroscopic (flow) behavior is required for a full description.

Embryogenesis: Embryonic development, the rise of a complex multicellular organism from a single fertilized egg, is a process that has fascinated people through the ages. How is it possible for cells, all originating from the same egg, to develop into a variety of highly specialized structures, such as muscles, skin, brain and limbs? What organizes the behavior of these cells, and how can the information encoded in the DNA account for the observed patterns and developmental processes? My lab studies embryogenesis in zebrafish and planaria (flatworms). Zebrafish embryos are a great model system for studying early vertebrate embryogenesis, as they are accessible to molecular biology and genetics, and ideal for imaging due to their optical transparency. While there has been great progress in elucidating the molecular components that play a role for cell motion during early gastrulation, little is known about the driving forces that allow for the observed large scale movements. Planarian embryogenesis is quite different from zebrafish in that embryos start out ectolecithal, i.e. yolk cells reside outside the embryo, and do not show real gastrulation movements. We are interested in studying the molecular and physical determinants for the morphogenetic processes occurring during planarian embryonic development.

Regeneration: Similar to embryogenesis, tissue differentiation and motion takes places at sites of wound healing and regeneration. However, regeneration and embryogenesis are different from in each other in that different molecules are expressed in embryos and adults and/or the same molecules may have very different roles. We are studying regeneration in planarians, which are members of the phylum Platyhelminthes, the flatworms. They share with vertebrates key traits such as bilateral symmetry, three germ layers (ectoderm, mesoderm, and endoderm), and dorsoventral and anteroposterior polarities. Planarians do not possess a true circulatory or respiratory system, but they display cephalization, a complex and well-organized accumulation of neurons in their anterior region. Planarian regeneration relies on the presence of adult stem cells, called neoblasts. Planarians consist of approximately 30% neoblasts, and according to the “father of the fruit fly”, T.H. Morgan, a piece 279th the size of the original worm is able to regenerate a fully developed new specimen. A tiny piece of tissue is thus capable of regenerating a fully functional new worm, with a new digestive system, nervous system and all!
Research on planarians has traditionally focused on surgical and pharmacological manipulations. Only recently, molecular methods such as in situ hybridizations, immunocytology, and RNAi have been successfully applied. By complementing the molecular methods with biophysics approaches and in vivo imaging, we hope to gain a deeper insight into the basic mechanisms accounting for regeneration and stem-cell regulation. Example questions we are interested in are the establishment of tissue polarity, scale and proportion, the physical forces at wound sites/wound closure and tissue fission.

Tools: For this research, we combine tools from physics, material science, molecular biology and genetics together with extensive in vivo imaging and theoretical modeling. We work towards a coherent picture between the cell and tissue dynamics and the underlying molecular machinery.