Our study on the type III CRISPR associated CalpL-T-S cascade has just been published in Nature. It’s an amazing story that started out of pure curiosity, when Christophe and Gregor decided to look into the structure and function of the enigmatic CalpL protease. The project really took off, when Niels joined the team and determined the crystal structure of CalpL alone and in complex with its activator cA4. Using bioinformatics, we figured out that the target of the protease is a small protein that we named CalpT. In a fantastic cooperation with the labs of Dmitri Svergun, Malcolm White, Bela Bode and Jonathan Schmid-Burgk we unraveled how the activation of CalpL works and that its target, CalpT, is an anti sigma factor that inhibits the third protein from the operon, the sigma factor CalpS. In the end, the CalpL-T-S cascade provides a direct connection between type III CRISPR mediated foreign RNA detection and the transcription machinery of the cell.