Stem cells have the remarkable ability to remove old proteins on cue and radically reshape the proteome as they assume highly specialized functions. But how do cells remove pre-existing proteins? How do different cell types tailor the proteome to their highly specialized physiology? How do mutations in the underlying machinery cause developmental disorders? In the Muhar lab we explore these questions by combining high-throughput genetics, proteomics and chemical biology tools.
In a recent project, we discovered how cells scan their proteome for chemical scars that mark oxidatively damaged proteins. This mechanism provides a rationale for how cells can colletively remove damaged or old proteins. In our future work, we aim to understand the role of this pathway in neural stem cells and differentiation. In addition, we will employ CRISPR-based genetic screens to understand how proteome remodeling is coupled to stem cell activity and cell fate decisions. In parallel, are developing genetic tools to measure protein turnover across diverse cell types.