About Student Research

Lori Lebruska (1995–1999)

In vitro selection of RNAs that bind and inhibit DNA-binding proteins

After receiving a degree in nutrition from Arizona State University, and service in the military, Lori Lebruska joined Mayo Graduate School and did her Ph.D. thesis training in the area of in vitro selection of RNA aptamers from vast random RNA libraries. Aptamers are small folded RNAs whose shapes are selected on the basis of their ability to bind to a target of interest. The resulting RNA "antibodies" are small and can be expressed within living cells as possible tools in research or therapy.

Lori's work opened an area of research asking if RNAs could mimic DNA and act as competitive inhibitors of DNA binding proteins, specifically transcription factors. Lori selected the important NF-kappaB family of transcription factors as targets for her selections. These proteins regulate development, inflammatory gene expression, HIV replication, and tumor cell resistance to chemotherapy and radiation. Lori performed in vitro selection experiments with recombinant NF-kappaB p50 homodimer protein, isolating an aptamer that binds the target protein with nanomolar affinity, and acts as a decoy for the transcription factor in vitro. Biochemical characterization set the stage for later structural studies of this molecule that eventually demonstrated that Lori had found a remarkable RNA that is able to mimic the structure of DNA.