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We ask how cells maintain their proteins in a functional and balanced state, through pathways collectively named the proteostasis network. Our goal is to understand how this network functions in human cells, and how it is challenged and rewired in disease states. A major focus are cellular mechanisms controlling protein aggregation and prion-like spread in neurodegenerative diseases.
Our functional genomics technology, which integrates CRISPR/Cas9-based control of gene function and large-scale genetic interaction maps, enables us to elucidate context-dependent networks and to pinpoint nodes that are potential therapeutic targets. We use biochemistry, biophysics and cell biology to "zoom in" on individual nodes to reveal their mechanism of action.