Gene silencing through RNA interference (RNAi) has emerged as a powerful tool for understanding gene function. Over the past several years, high-throughput RNAi screens have illuminated a wide variety of biological processes, ranging from genes that affect the activity of therapeutic agents to novel components of signaling pathways. For example, on Nov. 25, 2013, NIH announced that scientists have used RNAi technology to reveal dozens of genes that may represent new therapeutic targets for treating Parkinson’s disease. The research was published online in Nature.
NIH established a state-of-the-art RNAi screening facility that accepts proposals from any NIH researcher. The staff at this facility, administered by the NCATS Division of Pre-Clinical Innovation, assist investigators with all stages of project planning and execution, beginning with assay development through genome-wide siRNA screens, informatics/pathway analysis and rigorous follow-up. Genome-wide siRNA screens for humans and mice are available. Also routinely included in screens are miRNA mimic and inhibitor libraries.
Scott Martin, Ph.D., Group Leader, RNAi Screening
Eugen Buehler, Ph.D., Group Leader, Informatics
Pinar Ormanoglu, Research Scientist
Yu-Chi Chen, Research Scientist
Carleen Klumpp-Thomas, Automation Engineer
Hasson, S.A., Kane, L.A, Sliter, D.A., et al. Genome-wide high-content RNAi screens indentify regulators of parkin in selective mitophogy. Nature. In press.
Welsbie, D.S., Yang Z., Ge Y., et al. Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death. PNAS. 2013;110:4045–50.
Sivan, G., Martin, S.E., Meyers, T.G., et al. Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. PNAS. 2013;110:3519–24.
Buehler, E., Chen, Y.C., Martin, S.E. C911: A bench-level control for sequence specific siRNA off-target effects. PLoS ONE. 2012;7:e51942.
Pouliot, L., Chen, Y.C., Bai, J., et al. Cisplatin sensitivity mediated by WEE1 and CHK1 is mediated by miR-155 and the miR-15 family. Cancer Res. 2012;72:5945–55.
Marine, S., Bahl, A., Ferrer, M., et al. Common seed analysis to identify off-target effects in siRNA screens. J Biomol Screen. 2012;17:370–8.
Buehler, E., Khan, A.A., Marine, S., et al. siRNA off-target effects in genome-wide screens identify signaling pathway members. Sci Rep. 2012;2:428.