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Integrative Structural and Computational Biology

Ian J. MacRae, Ph.D.

Professor
Department of Integrative Structural and Computational Biology
California Campus
Laboratory Website
macrae@scripps.edu
(858) 784-2932

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

RNA interference (RNAi) is a broad-spread mechanism of gene silencing that plays a fundamental role in many aspects of eukaryotic biology including viral defense, developmental timing, stem cell division, memory and learning. We are interested in understanding the molecular mechanisms underlying RNA interference (RNAi) and related RNA silencing processes. Our approach is to combine techniques in structural biology with biochemistry and cell biology in order to understand the mechanistic details of RNAi.

On the molecular level RNAi is mediated by a family of ribonucleo-protein complexes called RNA-Induced Silencing Complexes (RISCs), which silence genes by mediating translational repression and degradation of targeted message RNAs. The versatility and power of RNAi arises from the fact that RISC can be programmed to target any nucleic acid sequence for silencing. RISC programming is therefore a critical cellular function, requiring the action of a specialized macromolecular assembly called the RISC-loading complex (RLC). Our current research is focused on illuminating the structure and catalytic mechanism of the RLC with the hope that this knowledge will facilitate the development of RNAi-based therapeutics for the treatment of human disease.

Education

Ph.D., Molecular & Cellular Biology, University of California, Davis, 2002

Selected References

MacRae, I.J., Ma, E., Zhou, M., Robinson, C.V., and Doudna, J.A. (2008) In vivo reconstitution of the human RISC-loading complex. Proc. Natl. Acad. Sci. 105:512-517.

MacRae, I.J., Zhou, K., and Doudna, J.A. (2007) Structural determinants of RNA recognition and cleavage by Dicer. Nature Structural and Molecular Biology 14:934-40.

MacRae, I.J., Zhou K, Li, F., Repic, A., Brooks, A.N., Cande, W.Z., Adams, P.D. and Doudna, J.A. (2006) Structural basis for double-stranded RNA processing by Dicer. Science 311:195-198.