Targeted Protein Degradation

The controlled degradation of proteins is essential for cellular function and fitness in all organisms, yet not fully understood. The consortium of thirteen research groups that comprise the SFB in ‘Targeted Protein Degradation’ aims to uncover the molecular mechanisms of cellular proteolytic pathways, among them the ubiquitin-proteasome system (UPS) and autophagy.

Achievements in the first funding period of the SFB include a better understanding of how giant E3 ubiquitin ligases, notorious for the challenges they present for their study due to their large size, recognize their substrates. The consortium also revealed new players in the subcellular localization of the UPS to the nucleus and acquired insights into the mechanisms by which the autophagy machinery identifies its targets. Furthermore, scientists from the SFB discovered new modalities for the action of molecular glues in reprograming E3 ligases for the inducible degradation of proteins, which has major implications for the design of novel therapeutics.

The second funding period will build on these discoveries. The major focus remains the targeted degradation of proteins by the UPS and autophagy in the cytoplasm and the nucleus. However, the consortium will expand research to other cell organelles. In addition, the consortium will expand their portfolio of techniques to include in vivo cross-linking and limited proteolysis mass spectrometry.

The SFB in its second funding period includes the research groups of Sascha Martens, Andreas Bachmair, Elif Karagöz, Alwin Köhler, and Gijs Versteeg at the Max Perutz Labs, Tim Clausen and David Haselbach at the IMP, Yasin Dagdas and Silvia Ramundo at the GMI, Noelia Urbán at the IMBA, Georg Winter at CeMM, Christian Becker at the University of Vienna as well as Ilaria Piazza at the Max Delbrück Center in Berlin. The total funding for the 8-year duration of the project amounts to €11 million.

Read more about the individual subprojects within the SFB here.