Riboswitches and Nucleic Acids Biochemistry
Our laboratory conducts experiments on naturally occurring and synthetic nucleic acids sequences. Our interest is in the mechanism of action as these biomolecules perform binding and catalysis events. We use standard molecular biology techniques and incorporate advanced optical methods to analyze the kinetics and thermodynamics of the interactions.
Ribonucleic acid (RNA) was, until recently, thought of as being relegated to the role of genetic middleman between DNA, the genome, and proteins, the workhorse of biology. However, the known roles of RNA in biology have been expanded dramatically with the discovery that RNA itself can impact DNA replication, transcription elongation, RNA processing, and translation initiation among other processes.
Riboswitches are untranslated RNA segments functioning as genetic control elements by binding a target metabolite and controlling the expression of genes associated with the biosynthesis or import of the target metabolite or a closely related molecule. Simply, a riboswitch is a naturally occurring aptamer appended to a gene express ion platform. Riboswitches are found in all three kingdoms of life and represent a fundamental and energetically conservative form of genetic control, yet this RNA-based genetic control mechanism was discovered only several years ago.
Further, both single-stranded RNA (ssRNA) and ssDNA sequences can be evolved in the test tube to perform binding and catalysis events. In vitro selection has proven to be a powerful method of developing biosensors to target molecules of interest to health care professionals and military analysts.
Our collaborators in this field include labs at Yale University, the University of Maryland-College Park, Carnegie Mellon University, the National Institute of Health, and the Walter Reed Army Institute of Research. We’ve been funded by DARPA, ARL, and the DMRDP through MRMC.