Dr. Nicholas R. De Lay
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Microbiology and Molecular Genetics
One of the ways that bacteria rapidly adapt to environmental changes or deal with stressors is to alter gene expression at the posttranscriptional level using small noncoding RNAs (sRNAs). sRNAs regulate gene expression by altering mRNA stability and/or translation by base-pairing with near complementary sequences within those mRNAs. This process of sRNA-mediated regulation is critical for the virulence and antibiotic resistance of many bacterial species including uropathogenic Escherichia coli, which causes the vast majority of urinary tract infections in humans. Thus, understanding this process of sRNA-mediated regulation may lead to the development of compounds that can be used to treat bacterial infections. Using E. coli as a model system, my lab is focused on how sRNA-mediated regulation works, why it works this way, and how we can inhibit this process. In order to understand the molecular mechanism of sRNA-mediated regulation, we have been identifying and subsequently characterizing proteins involved in this process. For example, I identified another factor, polynucleotide phosphorylase (PNPase), which in addition to Hfq is required for sRNA-mediated regulation. I have found that PNPase like Hfq is important for protecting sRNAs from degradation prior to pairing with target mRNAs.
There are several different projects that I would be interested in having graduate students take on. One project is to characterize the molecular mechanism by which PNPase protects sRNAs from degradation, and determine and characterize additional roles it may have in sRNA-mediated regulation. Another project for a student is to identify and characterize additional proteins involved in sRNA-mediated regulation. A third project is to identify and characterize molecules that inhibit this process.