Brian Lee's Research

The human microbiome has profound effects on human health including the response to infectious diseases, metabolism of nutrients, and mental health. Probiotic, lactic acid bacteria are a part of the microbiome that we can control through the consumption of fermented foods, such as yogurt and cheese.

Our research focuses on RNA regulatory elements that allow these probiotic bacteria to adapt to us as their host and influence our health. Previously, we identified a small regulatory RNA (sRNA) in Streptococcus thermophilus that we named AsdS due to its proximity to the asd gene for aspartate semialdehyde dehydrogenase. The AsdS sequence and predicted structure share homology with the MarS sRNA found to the human pathogen, Streptococcus pyogenes, where it regulates the expression of virulence genes including the antiphagocytic M protein found on the cell surface.

Recently, we have expanded our studies to include sRNA genes in Lactobacillus species. The ThrS sRNA was initially identified as a novel regulatory structure in Lactobacillus, but our studies have shown the core elements are strikingly similar to AsdS. The UspS sRNA is associated with the universal stress protein in Gram-negative Lactobacillus species and has some homology to 6S sRNA, which regulates RNA polymerase activity in Gram-positive bacteria. Lastly, we have also focused on a cis-acting element in the 5′ untranslated region of the gene for a tRNA/rRNA methyltransferase found in S. thermophilus.

We aim to identify additional sRNA transcripts that regulate bacterial metabolism and host interactions. In addition to sRNA transcripts, we will also characterize the extracellular vesicles produced by probiotic lactic acid bacteria that mediate effects on the immune system, the brain, and other host systems. Our long-term goal is to improve our understanding of the effects of these probiotics on human health.