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SFB 1324:  Mechanisms and functions of Wnt signaling

Subject Area Biology
Term since 2017
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 331351713
 
Wnt signaling pathways play a decisive role in development, cell differentiation and regeneration. Aberrant regulation of Wnt signaling can lead to severe developmental defects and diseases, including tumorigenesis. Wnt ligands are secreted, lipidated proteins that bind to half a dozen different receptors to activate multiple downstream signaling cascades. Wnt pathways relay signals from divergent ligand-receptor interactions to a network of downstream signaling of conserved cytoplasmic factors. Despite having gained an enormous amount of knowledge about components and mechanisms of Wnt signaling, we are now facing a multitude of new questions about the specificity of signaling input and the control of signaling output during development and in disease. Because Wnt signaling is of crucial importance for so many biological processes and diseases, the overarching and long-term goal of the Collaborative Research Center 1324 is to gain a mechanistic understanding of Wnt signaling and to investigate its physiological consequences in a representative spectrum of model systems. To advance our understanding of molecular mechanisms governing Wnt signal transduction, the Collaborative Research Center 1324 is structured into two major research areas: (A) Wnt secretion and receptor-ligand interactions and (B) Wnt coupling to downstream and context-dependent signaling. In the first research area, we want to understand how Wnt ligands are produced, how they are modified and how they are transported into the extracellular space. We also want to unravel the Wnt ligand receptor interactions and understand how they specify the signaling response and induce different signaling cascades. In the second research area, we will focus on the molecular dynamics of the Wnt machinery to understand how different Wnt pathways elicit distinct biological responses and how Wnt signaling is coupled to different downstream factors. We also want to understand the spatio-temporal dynamics of Wnt signaling, i.e., how Wnt signaling regulates oscillations and wave patterns. To address these questions, we will combine a wide range of model systems including hydra, fly, fish, frog, as well as mouse and human cells with cutting-edge technologies including advanced fluorescence microscopy, genetic screens and genome engineering, and proteomics. In the Heidelberg area we are in the unique situation to have a high density of research groups working on Wnt signaling, including international leaders in the field. In the second funding period, we will continue our successful project. In the second funding period, we will build on this success and will have a particular focus on the spatial and temporal control of Wnt signaling activity. The Collaborative Research Center will continue to dissect this key signaling pathway controlling the development of all metazoan animals and which plays pivotal roles in many human diseases.
DFG Programme Collaborative Research Centres

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Spokespersons Professor Dr. Michael Boutros, since 7/2021; Professor Dr. Thomas W. Holstein, until 6/2021
 
 

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