Targeted Protein Degradation
Groups Bachmair Becker Clausen Dagdas Haselbach Karagöz Köhler Martens Piazza Ramundo Urbán Versteeg Winter Previously a member: Beli Previously a member: Loizou

Group Piazza

Rewiring of the UPS network upon REDOX stress

Group Leader

Ilaria Piazza

Ilaria Piazza is a group leader at the Max Delbrück Center for Molecular Medicine in Berlin. Ilaria conducted her PhD studies at EMBL Heidelberg and then moved for a post-doc at ETH Zurich before starting her own research group.

 

Since 2024 Ilaria Piazza is member in this collaborative Special Research Program.

Projects within consortium

The ubiquitin proteasome system (UPS) is an effective clearance system to remove damaged unfolded proteins that could lead to disease and to regulate the physiological lifetime of protein substrates. In the UPS, ubiquitinated molecular targets for proteasomal degradation are recognized by E3 ligases, and the control of proteostasis occurs through specific interactions between pairs of E3 ligases and protein substrates. This project aims to identify and characterize new molecular glues with a systems biology approach. We will globally map protein-protein interactions and protein-small molecule interfaces using structural proteomics.

Structural proteomics can provide information on protein-protein interactions (PPIs) and protein binding interfaces. It is gaining interest in the field of drug development, particularly for PPI-targeting drugs. In this project we aim to advance structural proteomics technologies and their ability to provide insights into PPI networks and protein binding interfaces in complex biological samples. As a proof of principle, we will investigate how cellular stress influences the E3 ligase interaction network with a particular focus on the HECT domain protein HUWE1 and its interaction partner HAPSTR1 in in a variety of tissues including neural stem cells. After obtaining information about binding interfaces between substrates and degrading E3 ligase, we will test their druggability with ligands using chemical biology screens with our consortia partners at CeMM.

 

References:
https://doi.org/10.1016/j.sbi.2023.102648
https://doi.org/10.15252/msb.202110442

An overview of structural proteomics technologies: Figure from: https://doi.org/10.15252/msb.202110442

Project members

  • PhD student

    Maximilian Hornisch

    Affiliated

Targeted Protein Degradation related publications by Group Piazza

  • 2023 The potential of cross-linking mass spectrometry in the development of protein–protein interaction modulators Current Opinion in Structural Biology Ruwolt M, Piazza I, Liu F Go to publication →
  • 2021 The rise of proteome‐wide biophysics Molecular Systems Biology Mateus A, Savitski MM, Piazza I Go to publication →