Organs and specific cell types execute specialized functions in multicellular 
organisms, in large part through customized gene expression signatures. Thus, 
profiling the transcriptomes of specific cell and tissue types remains an 
important tool for understanding how cells become specialized. Methodological 
approaches to detect gene expression differences have utilized samples from 
whole animals, dissected tissues, and more recently single cells. Despite these 
advances, there is still a challenge and a need in most laboratories to 
implement less invasive yet powerful cell-type specific transcriptome profiling 
methods. Here, we describe the use of the Translating Ribosome Affinity 
Purification (TRAP) method for C. elegans to detect cell type-specific gene 
expression patterns at the level of translating mRNAs. In TRAP, a ribosomal 
protein is fused to a tag (GFP) and is expressed under cell type-specific 
promoters to mark genetically defined cell types in vivo. Affinity purification 
of lysates of animals expressing the tag enriches for ribosome-associated mRNAs 
of the targeted tissue. The purified mRNAs are used for making cDNA libraries 
subjected to high-throughput sequencing to obtain genome-wide profiles of 
transcripts from the targeted cell type. The ease of exposing C. elegans to 
diverse stimuli, coupled with available cell type specific promoters, makes TRAP 
a useful approach to enable the discovery of molecular components in response to 
external or genetic perturbations.