In 2007, Sebastian Schornack, then a freshly minted Ph.D. student from the laboratories of Thomas Lahaye and Ulla Bonas at the Martin-Luther-University Halle-Wittenberg, was fastidiously carrying out follow-up experiments to his thesis work. For the past few years he had been studying how the bacterium Xanthomonas infects its plant hosts. Specifically, he was interested in a class of “effector” proteins, called transcription activator-like (TAL) effectors, that the bacterium delivers to the nuclei of host cells to alter plant gene expression. Ever since their discovery in the late 1980s, the unusual structure of these effector proteins has intrigued plant microbiologists. TAL effectors contain many near-perfect repeats 34 amino acids in length with two hypervariable residues, but the biological meaning of this peculiar modular structure was unknown. At the time Schornack was finishing his thesis, TAL effectors had just been discovered to bind specific DNA sequences in the genomes of their host plants, where they activated expression of host genes thought to favour colonization by the pathogen. While comparing the identity of the hypervariable amino acids in the repeats of particular TAL effectors with the corresponding DNA sequence of their binding sites, Schornack experienced a flash of insight, and noticed a defining pattern. Following discussions with Jens Boch and experimental work with their colleagues at Halle University, it became evident that, indeed, a “code” built into the TAL effector proteins determines their DNA binding specificity. Not long after that, across the Atlantic, another Ph.D. student Matt Moscou, working with Adam Bogdanove at Iowa State University, independently reached a similar conclusion using clever computational analyses of TAL effector-induced expression changes in rice plants.
Both teams immediately grasped the impact of their discoveries – synthetic TAL effectors could be custom designed to bind any target DNA sequence. Such a technological breakthrough would have far reaching implications in biotechnology.