Grant: Project Grant

Bacterial resistance to antibiotics has become a global medical concern as shown by recent reports on the rise of highly drug resistant bacterial strains. Although this resistance was predictable, research to identify new antibiotics or cellular drug target has dropped drastically. Furthermore, many of the most commonly used and often last resort antibiotics have debilitating side effects. In stark contrast, we now appreciate that microbes in human microbiomes play crucial roles in maintaining good health. It is now clear that commensal bacteria in the intestine of mammals accomplish many beneficial functions. Although symbiotic bacteria and mammals have co-evolved and adapted to each other, the ecological niche offered by the host is plagued with environmental insults, to which the bacteria need to adapt rapidly and continuously. In response to stressful environment, bacteria express small regulatory RNAs to coordinate gene expression and adapt to various stress. Our recent work with small regulatory RNAs strongly suggest there is a large amount of unknown yet significant RNA-RNA interactions within bacterial cells. These interactions might regulate virulence and pathogenicity as well as antibiotic resistance. We will map the global RNA-RNA interactions quantitatively within the model bacterium E. coli as well as the major human pathogen Salmonella. Concurrently with this long-term goal, we will investigate the most promising RNA-RNA interactions to establish novel mechanisms of gene expression. We already have established the extended interactome of a few specific sRNAs in E. coli using a novel approach that we developed in the lab. Deciphering the most critical RNA-based regulations (including sRNA-mRNA, mRNA-mRNA, tRNA-mRNA), in bacterial cells. New RNA-RNA interactions are creating specific targets to test novel RNA-based therapies for medical doctors, pharmaceutical companies and drug developers.