Exploring transcription regulation through cell-to-cell variability

Yay! A paper that was in the works for two years, including more than six months in review, finally appeared in Proceedings of National Academy of Sciences, USA.

This describes Ruty's MSC dissertation, which was done with help from Ariel and me. In this work she took a very large dataset collected by Martin Jonikas and Maya Schuldiner at Jonathan Weissman's lab, and reanalyzed it to uncover new findings.

The key point of the paper is the use of "noise" or variability in expression levels of the same protein between genetically identical cells as a phenotype for genetic screen. Ruty shows that mutations that lead to abnormally high or abnormally low variability are involved in key processes in regulating transcription. Moreover, by using double knockouts she can pinpoint some mechanisms on these defects.

This work is cool as it shows that promise for the general theme that we want to pursue in the lab, of using genetic perturbation and examining effect on protein expression in single cells.