Professor Steffen Scholpp

Tissue development is a key process for life, starting from the earliest embryonic stages, during which cells differentiate into later organs composing an entire body. An essential component for these developmental processes but also for tissue regeneration and stem cell regulation is the communication of cells by chemical signalling. The highly conserved family of Wnt proteins represents essential regulators of cell behaviour, tissue development and homeostasis by inducing responses in a concentration-dependent manner. We identified a novel way of spreading Wnt proteins in vertebrates: Wnt molecules are mobilized on specific cell protrusions known as cytonemes. These specialized signalling filopodia transmit signal proteins between communicating cells and allow a high degree of control of propagation speed, direction and concentration of the transmitted ligand. The signalling molecules are delivered directly to the receiving cells by a direct-contact model, and parameters such as cytoneme length or speed of filopodia formation dictate local Wnt concentration.

In our research, we use the zebrafish embryo to investigate how intercellular Wnt protein transport is regulated and how signals are subsequently delivered to the target cell in a living vertebrate organism. By understanding Wnt dissemination mechanisms, we will be able to control Wnt signalling in development and regeneration. This research is funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

We further use gastric cancer cells to investigate how cytonemes mobilize Wnts in tumour tissue. Our research will open up new strategies to control Wnt signalling by altering its transport route in the tumour microenvironment. Our research is supported by the Medical Research Council (MRC).

At the Living Systems Institute, we collaborate with biophysicists using super-resolution microscopy to describe these signalling processes in a quantitative way on a molecular level. As it is very difficult to determine the specific impact of individual parameters in a complex biological system by a purely experimental approach, we interact with mathematicians using computational modelling. Together, we develop a robust mathematical model for the distribution of signal molecules on the basis of signalling filopodia. Due to the conserved nature of vertebrate cell behaviour, our results will be relevant to Wnt signalling during human embryonic development and could suggest novel vulnerabilities to Wnt-dependent diseases – a prerequisite for developing novel therapeutics.

CV

Since 2023 Professor of Cell and Developmental Biology (Personal Chair), Biosciences, University of Exeter, UK

2017-2023 Associate Professor of Cell and Developmental Biology, Biosciences, University of Exeter, UK

2009-2016 Emmy-Noether group leader (Assistant Professor) at the Karlsruhe Institute of Technology (KIT), Germany

2004-2009 Postdoctoral Research Fellow with Prof Andrew Lumsden, FRS, MRC Centre for Developmental Neurobiology, King’s College London, UK

2003-2004 Postdoctoral Research Associate with Prof Michael Brand, Max Planck-Institute of Cell Biology and Genetics (MPI-CBG), Dresden, Germany

2003 PhD Neurobiology (Hons., summa cum laude), University of Heidelberg, Germany

1999-2003 PhD student in Neurobiology (Laboratory of Prof Michael Brand), University of Heidelberg, Germany and Max Planck-Institute of Cell Biology and Genetics (MPI-CBG), Dresden, Germany

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