Understanding Ubiquitylation: From Molecular Mechanisms to Disease
The posttranslational modification of proteins by ubiquitin ("ubiquitylation") has taken center stage in eukaryotic cell biology. Ubiquitylation triggers the degradation of damaged proteins, cell cycle regulators, transcription factors and metabolic enzymes by the 26S proteasome. Moreover, it serves as a versatile mark in many non-proteolytic processes such as DNA damage repair, receptor signaling and endocytosis. Importantly, abnormalities of the ubiquitin system causally contribute to the pathogenesis of multiple human diseases including cancer, neurodegenerative disorders and infectious diseases. In many cases, however, neither the precise function of the affected ubiquitin system component in healthy individuals nor details of the pathogenesis following its impairment are known. These limited mechanistic insights constitute an obstacle to the design of efficient therapeutic strategies and emphasize the requirement for continued efforts in basic research.
The research focus of the research training group GRK 2243 is the elucidation of biochemical and pathogenic mechanisms underlying diseases that are linked to the ubiquitin system. The research program is aimed at generating a thorough mechanistic understanding of disease-relevant enzymes of the ubiquitin system, which will guide the subsequent molecular and cellular analysis of the pathogenic consequences of their malfunction. The long-term objective of the GRK 2243 is the identification of novel strategies for the therapy of ubiquitin-related diseases.
There is a growing demand for highly qualified scientists with excellent knowledge of the molecular basis and the biomedical aspects of protein ubiquitylation. The training program of the GRK 2243 is therefore aimed at instructing doctoral researchers in a wide spectrum of state-of-the-art and emerging methods and concepts in ubiquitin research covering structural biology, biochemistry, molecular cell biology, tumor biology, microbiology, functional genomic screens, in silico drug design and proteomics in an internationally competitive scientific environment.