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Correspondence to: michael.mcmanus@ucsf.edu
The project was conceived and directed by M.B. and M.T.M.
Screen optimisation was performed by M.B. and D.W.
Libraries were designed by J.A.B. with guidance from M.B. and cloned by M.B.
Orthogonal vectors and cell lines were created by M.B.
All screens were performed by M.B., with A.B. assisting in CRISPRa screen analysis.
R.T. developed the computational pipelines and the statistical framework for data analysis for screens with guidance from M.K. R.T. also selected the best-performing sgRNAs for arrayed validation.
M.B. and R.T.W. conducted and analysed arrayed validation experiments.
E.M. and R.T.W. performed western blot analyses.
X.M. and H.F. conducted and analysed TR-FRET experiments.
M.B. and M.T.M. wrote the manuscript with critical input from R.T., M.K., N.Z. and F.M.
All authors read and approved the final manuscript.
Special thanks go to members of the McManus Lab who provided critical feedback during the course of this project and Elizabeth Cahill for excellent technical support.
We also thank Luke A. Gilbert and Marvin E. Tanenbaum for sharing the CRISPRa cell line ahead of its publication.
The authors declare no competing financial interests.
M.T.M. was supported by NIH/CTD2 (U01CA168370) and IDG (1U01MH105028).
M.K. was supported by NIH/NIGMS New Innovator Award DP2 GM119139, NIH/NCI K99/R00 CA181494, a Stand Up to Cancer Innovative Research Grant and the Chan Zuckerberg Biohub.
J.B. was supported by NIH Training grant T32 GM00715 and an AFPE Predoctoral Fellowship.
H.F. was supported by NIH/CTD2 (U01CA168449).
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