The Yeast Two-hybrid Assay

No protein is an island.

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Y2H Milestones

No protein is an island. They're linked by complex networks, and many cellular processes – transcription, translation, mitosis, and motility, to name but a few – are the work of complex macromolecular machines. Researchers keen to figure out how proteins interact were for many years hamstrung by relatively crude, and labor-intensive, analytical tools. Then, in the late-1980s, a new option emerged: the yeast two-hybrid (Y2H) assay.

The brainchild of Stanley Fields, a Howard Hughes Medical Institute investigator at the University of Washington, Y2H is a genetic method that relies on the modular architecture of transcriptional activators to identify protein-protein interactions in the yeast nucleus.

At first, researchers used Y2H mainly to find partners for individual proteins. But by the year 2000, the scientific community had developed both the hardware (e.g., liquid-handling robots) and the intellectual capital (e.g., annotated genome sequences) necessary to take Y2H to the genomics level.

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