2003 Fifth Annual Beckman Scholars Symposium

"Selection of RNA Aptamers Against a Protein/Drug Composite Surface"

Kelly Plummer
1998 Beckman Scholar Alumni
BS - Chemistry, BS - Mathematics
University of Minnesota, Twin Cities
Presently, Ph.D. Program in Chemistry
Harvard University

In a number of natural systems, target binding is modulated via an intermediate ligand; the absence of this ligand consequently prevents a protein/protein interaction. Presentation of the composite surface of a ligand-bound protein to the target is required to elicit a biological effect. We are interested in using small organic molecules to mediate protein/RNA binding events. Specifically, we sought to identify RNA sequences capable of binding a protein target in a small molecule dependent manner. To this end, we have used in vitro selection to search a pool of 1015 individual RNA sequences for those that exhibited these properties. After seven rounds of iterative selection and amplification, we discovered aptamers that bound a protein/drug complex with nanomolar affinities. Neither protein nor drug has appreciable affinity for RNA alone. Systems such as these may provide tools to regulate gene expression and to study native protein/RNA interactions.

Kelly Plummer is currently a Ph.D. candidate in the Department of Chemistry and Chemical Biology at Harvard University. She completed a double major during her undergraduate studies at the University of Minnesota-Twin Cities, graduating in 1999 with high distinction in chemistry and magna cum laude in mathematics. While at the University of Minnesota, she worked in the lab of Professor Craig Forsyth to synthesize analogs of the natural product okadaic acid. She received numerous awards from the chemistry department, and in 1999 was awarded a National Defense Science and Engineering Graduate fellowship from the Department of Defense. At Harvard University, she works in Professor Greg Verdine’s lab to study small molecule-mediated interactions between proteins and RNA. She has been a teaching fellow for several undergraduate courses in organic chemistry and is currently a co-chair of Harvard Women in Chemistry. Her interests include sailing, volleyball and cross country skiing.