GRK 2415:  Mechanobiology in Epithelial 3D Tissue Constructs

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 363055819

The RTG Mechanobiology in Epithelial 3D Tissue Constructs (MEƎT) trains doctoral researchers in the research areas of mechanobiology and tissue engineering. The doctoral researchers examine how mechanical stimuli regulate tissue morphogenesis and remodeling, and influence disease progression, based on the hypothesis that the micromechanical niche determines cellular responses, which in turn modify the cell's mechanical niche. In the first period, we achieved a better understanding of the mechanobiological feedback between epithelia and their environment by combining cell biology with biofabrication of customized 3D constructs. The second period will use and expand the established scientific network and collected knowledge to examine molecular pathways and further develop responsive biomaterials and biofabrication methods to steer epithelial morphogenesis and study epithelial pathology. Cell biology, biophysics and bioengineering must work hand in hand to provide a toolbox to unravel fundamental mechanobiological mechanisms. MEƎT exploits the unique constellation at RWTH Aachen University bringing together engineers and life science researchers to create and combine novel biomaterials and cellular systems that are able to mimic and trigger mechanical stimuli in 3D tissue models. The doctoral researchers leverage this constellation to learn about designing biomaterials, production of 3D constructs and devices, and the mechanisms governing tissue mechanics. They exploit this knowledge for engineering tissue equivalents representing healthy and diseased states with the aim to control and monitor tissue mechanics at different time and length scales. Such complex tissue models are urgently sought by the pharmaceutical industry and academia for drug screening, reduction of animal use, and basic research. MEƎT concentrates on epithelia, which consist of tightly linked cells at mechanophysical boundaries that are exposed to tremendous mechanical stress and strain. The projects address fundamental aspects of epithelial mechanobiology focusing on: - epithelial differentiation and invasion by studying embryoid bodies, mechanisms of basement membrane breaching and uterine embryo implantation, - distribution and sensing of forces in multilayered epithelia by examining epidermal adaptation in response to mechanical load, wounding, and cytoskeletal perturbations, and by investigating epithelial-neuronal mechanosensing, - interaction between epithelia and their immediate environment to elucidate the importance of mechanical signals for inflammation, aging, and functional multi-tissue assembly. The research activities are embedded in a curriculum that is tailored to the interdisciplinary needs of the doctoral researchers and ensures acquisition of a comprehensive knowledge base. Dedicated mentoring, counseling, and personalized training support rapid completion of the doctoral projects as a solid foundation for successful future careers as innovative leaders.

• DFG Programme: Research Training Groups
• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Spokesperson: Professor Dr. Rudolf E. Leube
• Participating Researchers: Professor Dr.-Ing. Horst Fischer; Professor Dr. Stefan Jockenhövel; Professorin Dr. Angelika Lampert; Professorin Dr.-Ing. Laura De Laporte; Professor Dr. Andreas Ludwig; Professor Dr. Rudolf Merkel; Dr. Erik Noetzel-Reiss; Dr. Jacopo Di Russo; Professorin Dr.-Ing. Francesca Santoro; Professorin Dr. Ana-Suncana Smith; Privatdozentin Dr. Anja Lena Thiebes; Professor Dr. Stefan Uhlig; Professor Dr. Wolfgang Wagner