Ein innovativer Ansatz die funktionale Rolle epigenetischer Modifikationen in Stammzellen, neuraler Entwicklung und Gehirntumoren zu untersuchen.

• Antragsteller: Professor Dr. Stefan Stricker
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen ; Entwicklungsneurobiologie
• Förderung: Förderung von 2014 bis 2017
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 257151303

• Erstellungsjahr: 2020

Zusammenfassung der Projektergebnisse

The aim of the project was to investigate which role epigenetic processes play in the development of the nervous system and its diseases. Using a transgenic approach, we intended to analyse the immediate effects of loss of histone modifications through overexpression of histone mutants in mouse neural stem cells. Early in the implementation of the project, we deviated from the original experimental strategy due to emerging publications and budget restraints. Instead, we explored the options novel CRISPR approaches can provide for the investigation of epigenetic processes. In the context of the project, we have developed tools and strategies for epigenome editing and transcriptional engineering in the nervous system, developed tools and strategies for epigenomic screens and for gRNA multiplexing. Furthermore, we have introduced these experimental strategies (e.g. epigenome editing and transcriptional engineering) to a larger scientific audience. In summary, this project provides a solid base for the use of non-genetic CRISPR approaches for the investigation of epigenetic processes during development and disease of the nervous system.

Projektbezogene Publikationen (Auswahl)

• (2015). Brave new epigenomes: the dawn of epigenetic engineering. Genome Med 7, 59
  Köferle, A., Stricker, S.H., and Beck, S.
  
• (2016). CORALINA: a universal method for the generation of gRNA libraries for CRISPR-based screening. BMC Genomics 17, 917
  Koferle, A., Worf, K., Breunig, C., Baumann, V., Herrero, J., Wiesbeck, M., Hutter, L.H., Gotz, M., Fuchs, C., Beck, S., et al.
  
• (2017). A Universal Protocol for Large-scale gRNA Library Production from any DNA Source. JoVE, e56264
  Koferle, A., and Stricker, S.H.
  
• (2017). From profiles to function in epigenomics. Nat Rev Genet 18, 51-66
  Stricker, S.H., Koferle, A., and Beck, S.
  
• (2018). A Customizable Protocol for String Assembly gRNA Cloning (STAgR). JoVE, e58556
  Breunig, C.T., Neuner, A.M., Giehrl-Schwab, J., Wurst, W., Götz, M., and Stricker, S.H.
  
• (2018). DNA-Methylation: Master or Slave of Neural Fate Decisions? Front Neurosci 12, 5
  Stricker, S.H., and Gotz, M.
  
• (2018). One step generation of customizable gRNA vectors for multiplex CRISPR approaches through string assembly gRNA cloning (STAgR). PLoS One 13, e0196015
  Breunig, C.T., Durovic, T., Neuner, A.M., Baumann, V., Wiesbeck, M.F., Koferle, A., Gotz, M., Ninkovic, J., and Stricker, S.H.