About Student Research
Susan Wurster (2005–2009)
Searching Vast Random Libraries of Small RNAs for New Inhibitors
Arriving at Mayo Graduate School in 2004 from her undergraduate engineering background at Oral Roberts University in Oklahoma, Susan Wurster was curious about molecular biology projects that linked engineering principles and drug discovery. In the Maher lab she initiated a study involving the creation and characterization of RNA "aptamers," small folded and unnatural RNA molecules whose shapes allow them to stick tightly to specific molecular targets in cells. Like antibodies, it is the shape of aptamers that is crucial. Built entirely of RNA, aptamers can be expressed from genes that have been artificially placed in cells.
Susan's work builds on the projects of two prior Ph.D. students who demonstrated that small folded RNA molecules may inhibit DNA binding transcription factors by competing for the protein surface normally used to bind DNA. Such RNAs occur by chance in experimental "libraries" of more than 10,000,000,000,000 random 100-mer RNAs. Cycles of affinity selection and amplification are used to find these rare RNAs. Susan has identified new small RNAs that tightly bind to one of the subunits of a key human transcription factor, NF-κB, important in inflammation, HIV infection, and resistance to cancer therapy. Comparing these molecules with RNAs developed against other NF-κB protein subunits, Susan will be in the position to study their structure, mechanism of action, and ability to function as inhibitors within cells. One of Susan's goals is to determine if expression of RNA aptamers in an organism can inhibit the function of NF-κB-like proteins. She plans to use the genetic advantages of fruit flies for these experiments.