Ph.D., Stanford, 1978
Postdoctoral Research: MRC Laboratory of Molecular Biology, Cambridge, England
Address: 315B Biochemistry
Research InterestsThe molecular basis of RNA control: how it is accomplished, integrated and evolves, and how it is used during development and in the brain.
Research FieldsGene Expression
RNA control determines when, where and how
much protein is produced from an mRNA. Tens of thousands of mRNAs are
regulated in a single human cell, and the controls are pivotal in a wide
variety of biological contexts, from development to disease to learning
and memory. We want to understand, comprehensively and in molecular
detail, how mRNA regulation works: how the mRNAs are recognized, how
activators and repressors do what they do, and how they are used in
biology. We want to integrate that knowledge to understand the mRNA
regulatory circuitry of complex biological decisions.
We concentrate on factors and circuits that are found among all eukaryotes. We have developed facile genetic systems in yeast to identify new proteins from any organism that bind to RNA sequences of interest, or to analyze their function independent of their ability to bind RNA. The region of the mRNA between the termination codon and poly(A) − the 3' untranslated region (3'UTR) − is critical. We identify proteins with which 3'UTRs interact, and use that to put together and understand networks of RNA control. In parallel, we dissect the mechanisms through which those factors activate or repress mRNAs.
We work at the interface between molecular genetics, biochemistry, and developmental biology and neurobiology. We combine the molecular genetics of yeast and C. elegans with manipulations of frog embryos and cell-free systems. We combine biochemistry with biology and genetics to get a complete picture, and reveal which features are general and which are idiosyncratic. Currently, we focus on regulation of stem cells in C. elegans, the cell cycle in Xenopus embryos, and memory in Drosophila.
Goldstrohm and Wickens. In press. Multifunctional deadenylase complexes and the diversity of mRNA control. Nature Mol Biol Rev.
Kwak and Wickens. 2007. A family of poly(U) polymerases. RNA.13:860-867.
Suh, Jedamzik, Eckmann, Wickens and Kimble. 2006. The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line. Proc Natl Acad Sci USA 103:15108-15112.
Goldstrohm, Hook, Seay and Wickens. 2006. PUF proteins bind Pop2p to regulate messenger RNAs. Nature Structural and Molecular Biology. 13:533-539.
Opperman, Hook, DeFino, Bernstein and Wickens. 2005. A single spacer nucleotide determines the specificities of two mRNA regulatory proteins. Nature Structural and Molecular Biology. 12:945-951.