Research Interests

RNA polymerase, transcription factors, gene regulation, stress response, bacterial resistance, bacteria-host interaction, gasotransmitters, aging mechanisms

Research Statement

Our most significant contributions include:

  1. RNA polymerase “backtracking” and “ratcheting”: In 1997 we described back- and-forth sliding of RNAP along DNA and RNA. Our group then showed that this phenomenon, which we called “backtracking”, plays the key role in controlling gene expression and is a source of genome instability. We also demonstrated that RNAP is a Brownian ratchet machine. Our findings explained in mechanistical details how RNAP translocates, how it responds to regulatory signals and factors, and how it terminates transcription.
  2. Riboswitches: In 2002, we described the first ligand-sensing mRNAs that regulate biosynthetic genes in B. subtilis. Simultaneously, Ron Breaker reported similar findings in E.coli. Since then dozens of riboswitches have been described in many evolutionarily distant bacteria, with counterparts in archaea, plants, fungi, and algae, where they control numerous genes.
  3. Eukaryotic thermosensor: In 2006 we isolated a complex composed of the translation elongation factor eEF1A1 and a novel non-coding RNA (HSR1) that is required for activation of heat shock genes in mammals. We proposed that HSR1 serves as a molecular thermosensor. We then showed that eEF1A1 orchestrates the whole process of heat shock response, from transcription activation to mRNA stabilization, transport, and translation. These findings provide a new paradigm of cellular adaptation to stress, with far-reaching clinical implications.
  4. Bacterial gasotransmitters: We have shown that endogenously produced gases NO and H2S protect bacteria from oxidative stress, immune attack, and numerous antibiotics. These results provide an experimental support for the emerging concept of antibiotic killing, which relies on oxidative damage, and establish NO- and H2S-producing enzymes as promising new targets for antimicrobial therapy. We further showed that NO produced by bacteria inside C. elegans diffuses into animal’s tissues where it activates a defined set of genes that protect nematodes from environmental stress and extend their lifespan.

Selected Publications