Source: Interfolio F180
Ian MacRae, PhD
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, 2002B.S. (Biochemistry), Univ. California, Davis, 1996
Awards & Professional Activities
2012 Blasker Science & Technology Award2009 Baxter Foundation Young Faculty Award
2008 Pew Scholar in the Biomedical Sciences
2002 Life Sciences Research Foundation Postdoctoral Fellowship
Selected Publications
MacRae, Ian J.; Ma, E.; Zhou, M.; Robinson, C. V.; Doudna, J. A. In vitro reconstitution of the human RISC-loading complex. Proceedings of the National Academy of Sciences of the United States of America 2008, 105, 512-517.
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MacRae, Ian J.; Zhou, K.; Doudna, J. A. Structural determinants of RNA recognition and cleavage by Dicer. Nature Structural & Molecular Biology 2007, 14, 934-940.
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MacRae, Ian J.; Zhou, K. H.; Li, F.; Repic, A.; Brooks, A. N.; Cande, W. Z.; Adams, P. D.; Doudna, J. A. Structural basis for double-stranded RNA processing by Dicer. Science 2006, 311, 195-198.
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