The drama of biology is played out through thousands of protein-protein interactions. Historically, researchers could only examine these interactions one by one, but genomic sequences and high throughput methods have opened up the "interactome" - the complete list of all protein interactions in an organism.
With a sequenced eukaryotic genome, lists of every protein, and genetic amenability, Saccharomyces cerevisiae was an obvious model with which to examine cell-wide protein interactions. In 2000, Peter Uetz and colleagues, then at the University of Washington, made the first attempt at systematically mapping protein-protein interactions in yeast, reporting 957 putative interactions from 1,004 yeast proteins.
A smattering of similar studies soon followed, but they shared a flaw: the use of expression vectors that overproduced tagged proteins. It became clear that future work needed to maintain endogenous protein levels, says Jack Greenblatt, from the University of Toronto.
In 2006, back-to-back Hot Papers did this using ...
