TGFß/BMP signalling in space, time and function

Dr. Giorgos Pyrowolakis (CIBSS-AI), HMH and Institute of Biology I, University of Freiburg

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Tight spatiotemporal control of signaling activity allows building an extreme variety of signaling regimes matching the multitude of functional and biological output. The components accounting for such regulation are largely known, however, their exact mode of action and the mechanisms that enable the same set of regulators to adjust signalling outcome to the biological context are ill defined. We are using Drosophila TGF-ß signaling to understand how rewiring of regulatory networks and feedback circuitry enables diversified spatiotemporal pattern of signaling  - ranging from long-range morphogen gradients, to short-range and cell-contact dependent signalling or to fast temporal switches in signal branch activity. To this end, we establish and use novel nanobody-based strategies to grasp signal regulation at the level of the plasma membrane. In addition, we investigating transcriptional regulation by BMP signaling in order to (i) uncover tissue-specificity in BMP responses and (ii) be able to manipulate regulatory feedback by genome engineering and address the impact of regulatory feedback in signal regulation. We wish to reach a level of understanding that will allow us to manipulate regulatory topology in vivo and bring about predictable changes in signalling output and, consequently, in shape and form of organs, regeneration potential of tissues or properties of stem cells  niches.