Yuet, K.P. et al. Proc. Natl. Acad. Sci. USA. 112, 2705–2710 (2015).

Proteomics information is most useful when it comes from specific cell types. In small organisms such as the worm, it is hard to isolate cell types by sorting or microdissection methods. As an alternative, Yuet et al. present a method to tag proteins from specific cell types in Caenorhabditis elegans, allowing the proteins to be specifically enriched for proteomic analysis. The researchers express an engineered phenylalanyl-tRNA synthetase in a cell type of interest, permitting proteins in those cells to be labeled with the unnatural phenylalanine analog p-azido-L-Phe (Azf) by feeding bacteria labeled with Azf to the worms. This allows tagged proteins to be visualized through conjugation to probes that label the bioorthogonal Azf or to be enriched and subjected to quantitative mass spectrometry profiling. The approach could be used to build a cell-specific proteomic atlas of the worm and could potentially be adapted for other organisms.