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Research Training Group ProtPath

Understanding protease functions in cellular pathways through discovery and analysis of protease substrates

Proteases play key roles in most biological processes. Degradative proteolysis selectively removes proteins from the  proteome and is essential for protein quality control. In contrast, limited proteolysis 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 the pathomechanisms of devastating disorders. In consequence, proteases are inhibited by many currently used drug treatments and are attractive targets for innovative therapies. Therefore, the scientific range of protease research spans from structural biology and biochemistry to clinical science in a multidisciplinary approach requiring close interaction of open-minded and well-trained biomedical and clinical scientists. Although proteases have been known for more than 100 years, for many proteases still only few substrates are known and the complexity of cellular proteases as regulatory switches just starts to unfold.

To address those fundamental problems, 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, and what are the resulting cleavage products?

  3)  What is the consequence of the proteolytic events for cell function?

We envision to address those questions within an interdisciplinary research training program joining doctoral candidates of the natural (Dr. rer. nat./ PhD) and clinical (Dr. med./ MD) sciences.

Our RTG applies a wide range of model systems, synergistically covers multiple protease families as well as degradative and limited proteolysis, and seamlessly integrates novel omics-type techniques with fundamental biochemical and cell-biological experimental strategies. Doctoral researchers are guided during the transition from their basic medical studies or master degree to a broadly trained postdoctoral scientist with profound expertise in protease research that ensures successful careers in academia, medicine, or industry. This goes beyond project-related bench work and is based on a well-balanced course and supervision programme including dynamic mentoring and monitoring of thesis progress, acquisition of multidisciplinary practical and theoretical skills, local and international scientific exchange, as well as training of communication and ethical behaviour.