GRK 2606:  Understanding protease functions in cellular pathways through discovery and analysis of protease substrates (ProtPath)

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 423813989

Proteases play key roles in most biological processes. Degradative proteolysis selectively removesproteins from the proteome and is essential for protein quality control. In contrast, limitedproteolysis yields stable cleavage products with novel functionality or subcellular localization.The large number of proteases (e.g. 460 in humans) underpins their physiological importance.Malfunction and deregulation of cellular proteases are fundamentally involved in thepathomechanisms of devastating disorders. In consequence, proteases are inhibited by manycurrently used drug treatments and are attractive targets for innovative therapies. Therefore,the scientific range of protease research spans from structural biology and biochemistry toclinical science in a multidisciplinary approach requiring close interaction of open-minded andwell-trained biomedical and clinical scientists. Although proteases have been known for morethan 100 years, for many proteases still only few substrates are known and the complexity ofcellular proteases as regulatory switches just starts to unfold. To address those fundamentalproblems, the ProtPath RTG will focus on three key questions:1) How do proteases meet their substrates and how is specificity ensured?2) What are the substrates, what are the resulting cleavage products, and what is themode of cleavage (limited or degradative)?3) What is the consequence of the proteolytic events for cell function?We envision to address those questions within an interdisciplinary research training programjoining doctoral candidates of the natural (Dr. rer. nat) and clinical (Dr. med.) sciences. OurRTG covers a wide range of model systems, synergistically covers multiple protease familiesas well as degradative and limited proteolysis, and seamlessly integrates novel omics-typetechniques with fundamental biochemical and cell-biological experimental strategies. Doctoralresearchers are guided during the transition from their basic medical studies or master degreeto a broadly trained postdoctoral scientist with profound expertise in protease research thatensures successful careers in academia, medicine, or industry. This goes beyond projectrelatedbench work and is based on a well-balanced course and supervision programme includingdynamic mentoring and monitoring of thesis progress, acquisition of multidisciplinarypractical and theoretical skills, local and international scientific exchange, as well as training ofcommunication and ethical behaviour. To counter the widely discussed “replication crisis” inthe life sciences, the qualification program will have a strong focus on the 3R-principles of research,i.e. rigour, reproducibility, and robustness.

• DFG Programme: Research Training Groups
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Spokesperson: Professor Dr. Thomas Reinheckel
• Participating Researchers: Professor Dr. Matthias Eder; Dr. Ruth Geiss-Friedlander; Professor Dr. Olaf Groß; Professor Dr. Pitter Huesgen, since 1/2024; Professor Dr. Georg Häcker; Privatdozent Dr. Klaus-Peter Knobeloch; Professorin Dr. Claudine Kraft; Privatdozent Dr. Ulrich Maurer; Professor Dr. Chris Meisinger; Professor Dr. Oliver Schilling; Professorin Dr. Friederike-Nora Vögtle, until 12/2023