Recent studies have identified principle components of selective protein degradation, mediated by the ubiquitin/proteasome system (UPS). In all eukaryotes this pathway is pivotal for the degradation of naturally short-lived proteins such as cell cycle regulators and signal transducers and of misfolded or misassembled proteins. Therefore, it is not surprising that defects of the UPS often result in diseases of aging.
Our lab is interested in developmental processes regulated by the UPS using Caenorhabditis elegans as a multicellular model organism. Besides the already known E1, E2, and E3 enzymes, additional modulators for substrate recruitment and ubiquitin-chain assembly have been identified. We are interested to decipher the molecular mechanism of ubiquitin chain assembly in physiologically relevant pathways.
Development and maintenance of striated muscle relies on the turnover of regulatory and structural components. Recently, we identified a novel pathway that implicates myosin assembly and muscle maintenance in the pathophysiology of inclusion body myopathy (IBMPFD). But how protein aggregates and finally inclusion bodies are established is not understood at present. In addition to myofibre differentiation, we are interested in certain aspects of DNA repair/replication, which might be required to avoid accelerated aging. Our future studies will address this relationship between genome stability and developmental aging processes governed by ubiquitin.