Long non-coding RNA and Infection Biology
RNA is a truly remarkable molecule with functions and activities far beyond that of an intermediate information carrier. The abundant class of long non-coding RNAs (lncRNAs) contains highly specialized RNA with structural or regulatory functions that range from assembling large protein complexes to localizing, sequestering, or allosterically modifying proteins and other interaction partners. Our genome contains thousands of lncRNAs, many of which are specifically regulated during bacterial or viral infections. However, their contribution to launching and sustaining an effective host response remains elusive. Our group combines a cutting-edge suite of technologies from the fields of biochemistry, genomics, molecular biology, and computational biology to decode how lncRNA work mechanistically and how they contribute to host defense mechanisms.
To effectively combat invading pathogens, host cells need to be able to rapidly adjust their gene expression programs and mount an effective host response. In addition to messenger RNA (mRNA), thousands of so called long non-coding RNAs (lncRNAs) are actively transcribed and specifically regulated as a result of bacterial or viral infections. While lncRNA resembles their protein coding counterparts in length, splicing structure, and biochemical properties, they do not serve as templates for protein synthesis. Hence, their physiological functions and biochemical mechanisms are challenging to dissect and in many cases remain poorly understood.
Recent breakthroughs in DNA sequencing technologies led to the realization that many lncRNAs are potent regulators of various gene expression programs, including the host response to pathogens. Knowledge of hundreds to thousands of pathogen-responsive lncRNAs can be considered a treasure trove for discovering novel mechanisms of gene regulation and host defense strategies.
Our group aims to decipher the genetic code controlling lncRNA function by obtaining a quantitative understanding of their molecular interactions and decoding the sequence features or structural elements that mediate these interactions. We seek to elucidate the composition of lncRNA complexes and aim to identify biochemical interactions that enable lncRNA functions. In this context, we are particularly interested in broadly exploring our recent finding that lncRNAs can modulate proteins and control their ability to assemble higher-order ribonucleoprotein complexes. Our group is developing and applying cutting-edge technologies to characterize direct interactions of individual RNA species with proteins at high resolution and in a quantitative manner. Ultimately, we hope to utilize insights into the mechanisms of lncRNA function in order to improve our understanding and ability to treat infectious disease.