Richard A. Lease, Ph.D.
- Research Scientist and Principal Investigator, Department of Chemical and Biomolecular Engineering
- Lab Supervisor, Department of Chemistry & Biochemistry
- The Ohio State University
- Columbus, Ohio USA
Primary field of research: Genetics and Biophysics of Regulatory RNA: Structure, Function, and Application
Dr. Lease's Laboratory studies basic structure-function relationships and applications of bacterial small regulatory RNAs (sRNAs) in dynamic gene expression control. The sRNAs can antagonize translation by binding to mRNA translational regulatory sequences. Regulation by sRNA is dynamic and rapid because sRNAs are produced quickly, i.e., unlike regulatory proteins, no translation is required.
The mRNA to be regulated is specified by sRNA:mRNA base-pairing interactions, and altering these sRNA sequences can be used to retarget the sRNA activity. These sRNAs exert control on existing mRNAs to govern decisions between mRNA translation into proteins versus mRNA turnover (reduced protein synthesis).
Thus in principle any mRNA and its protein product levels can be targeted for novel, human-designed regulation by altering the modular antisense sequence in the sRNA. Synthetic biology applications of this work include the generation of gene knock-downs in industrially relevant but genetically less–tractable microbes such as Clostridium acetobutylicum, the fine-tuning of gene expression in fermentation cultures, and surveying the effects of knock-down variants on metabolism without knocking out individual genes.
We created an E. coli genetic system based on DsrA sRNA to test and retarget these sRNAs to different mRNAs, and succeeded in using it to generate semisynthetic re-targeted sRNAs that simultaneously regulate multiple mRNAs using modular stem-loop antisense regulatory motifs.
Our work on stem-loop antisense motifs led to testing their general function in sRNA:mRNA interactions and to consider their potential application for building self-assembling RNA nanostructures.