Stefan Rüdiger is Professor for Protein Chemistry of Disease. The Chair Protein Chemistry of Disease is dedicated to gather mechanistic insights into protein folding and cellular protein quality control, and to apply this knowledge to protein-folding related diseases. The group of Stefan Rüdiger aims to provide a molecular understanding of how cells ensure protein folding and homeostasis, and to exploit this knowledge for targeting protein folding diseases. A key achievement was identifying the general function of HSP90 chaperones as the downstream optimizer of the HSP70 chaperone system. Currently the Rüdiger group applies the insights on chaperone mechanism to protein quality control of disease. The group develop peptide-based compounds to target protein aggregates at the earliest possible stage (“Fibril paints”), as PROTAC-like drug leads. His team studies the accessibility of (patient-derived) protein aggregates for the protein quality control machinery. The Rüdiger group also advances the technological state-of-the-art to address biochemical proteostasis questions. A recent example is the application of flow-induced dispersion analysis (FIDA) to protein fibrils, which allows assessing growth and shrinkage of patient-derived protein fibrils upon interaction with protein quality control factors and drug leads.

A key challenge in molecular medicine is to develop cures for diseases for which no cure exists – such as Alzheimer, Parkinson, Huntington or ALS, but also many other diseases with dramatic impact for the affected individual such as ataxias or cystic fibrosis. These diseases have in common that the molecular cause is related to uncontrolled consequences of protein damage and aggregation. Our body is not unprotected against protein damage. The fidelity of protein shape in the cell is maintained by a powerful protein quality control network, in which molecular chaperones and proteases play a key role. This networks supresses the appearance of most folding related diseases for the best part of our life. However, why does it suddently fail when we get older? Why do some individuals get a protein-aggregation related disease and others do not? What is the impact of the protein quality network for the development of an entire organism? Can we boost the cellular defense system to prevent the origin of the disease, or at least prevent progress of the diseases for some cases? How can we exploit our molecular understanding of our knowledge to develop taylor-made compounds to target protein aggregation diseases, including Alzheimer or Huntington?

Rüdiger's group aims to understand protein folding processes in the cell and their consequence for the origin of fatal diseases, and to exploit this knowledge for the development of novel strategies for treatment of these diseases.

Manuscript Inaugural lecture (Oratie) "Art and Destiny", 2 Oct 2023:
R602 Oratio Rüdiger public 231112 1445h.pdf

Current and previous external research support
 

Gravitation programme FLOW (main applicant)
Nation-wide consortium to understand protein quality control in disease

Alzheimer Nederland (main applicant)
Major grant

Campagne Team Huntington (main applicant)
Full research grant

NWO - Nederlands Organisation for Scientific Research (PI): 
ZonMW TOP Grant "Chaperoning axonal transport in neurodegenerative disease"

ISAO  - Internationale Stichting Alzheimer Onderzoek (Main applicant)
https://www.alzheimer.nl/onderzoek/onderzoeksprojecten/chaperonnes-en-de-aggregatie-van-tau/detail

Marie-Curie ITN "WntsApp" (PI)
http://wntsapp.eu/projects/control%20of%20complex%20assembly%20in%20the%20WNT%20cascade
http://wntsapp.eu/projects/chaperone%20binding%20motifs%20in%20disordered%20WNT%20signalling%20proteins

Marie-Curie ITN-IDP "ManiFold" (Programme Leader and PI)
http://www.manifold-idp.nl/CHAPERONE%20BINDING%20MOTIFS%20IN%20DISORDERED%20PROTEINS
http://www.manifold-idp.nl/THE%20SUBSTRATE%20RECOGNITION%20SITE%20OF%20A%20CHAPERONE%20MACHINE

NWO Graduate Programme (Programme Leader)

NWO BAZIS equipment grant (Project Leader)

NWO VIDI grant (Main applicant)

Marie-Curie Excellence Grant (Main applicant)

Utrecht University High Potential Grant (Main applicant, joint grant with Dr Madelon Maurice, UMCU)

Current group members
Júlia Aragonés Pedrola
Franoise Dekker
Magdalena Wawrzyniuk
Iris Rots
Adriana Poza Rodriguez