Plenary 4.1

9/1 11:00 - 1:00, Memorial Auditorium

A caged morpholino-based strategy for transcriptional target discovery

James K. Chen

Professor of Chemical & Systems Biology, Stanford University.

Deciphering the molecular mechanisms that regulate vertebrate development and physiology requires an ability to alter these genetic programs with spatiotemporal precision. Caged morpholino (cMO) oligonucleotides enable light-controlled gene silencing in zebrafish and other optically transparent organisms, and we report here the application of cMOs to discover transcriptional targets of the T-box gene no tail (ntl). In contrast to previous whole-embryo analyses of the ntl-dependent transcriptome, we have identified ntl targets in a tissue-specific manner by combining cMOs, photoactivatable fluorophores, fluorescence-activated cell sorting, and microarrays. Using this strategy, we have discovered distinct sets of ntl-regulated genes that contribute differentially to notochord formation and maturation.

James K. ChenJames K. Chen, Ph.D. is an Assistant Professor of Chemical and Systems Biology at Stanford University. He received a Ph.D. in Chemistry and Chemical Biology from Harvard University in 1999 and completed his postdoctoral studies at the Johns Hopkins School of Medicine in 2003. His laboratory integrates organic chemistry and developmental biology to probe the molecular mechanisms of embryonic patterning, tissue regeneration, and oncogenesis. Dr. Chen's honors include a Kimmel Scholar Award, a March of Dimes Basil O'Connor Award, and an NIH Director's Pioneer Award. He is also the Executive Director of the Stanford High-Throughput Bioscience Center.