Human cells contain crowds of protein variants, but, especially in a time of funding challenges, chasing these proteoforms takes dogged persistence.
Biology delivers a massive number of puzzles to proteoform hunters1,2. Proteoforms are the droves of protein variants that one and the same gene can give rise to. This variant explosion takes place after DNA is transcribed to mRNA and a protein is synthesized. No single method currently lets researchers hunt these proteoforms reliably and at scale. Sparks fly in discussions about which of the existing approaches — ‘bottom-up’ or ‘top-down’ proteomics, shades thereof, or other, newer technologies — is most promising. Some rifts seem to be closing as scientists keep up their proteoform hunt in a tense funding environment.