The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

The main focus of research in our lab is to understand molecular recognition and mechanism of enzymes and protein toxins involved in RNA modifications and cleavages in a sequence dependent manner. In order to achieve this goal, we employ knowledge and techniques from a broad spectrum of areas, including biochemistry, chemical biology, molecular biology, and structural biology. Furthermore, the knowledge gained from these studies serves as a starting point, allowing us to design and engineer small proteins or organic ligands that are useful against certain lethal bacteria and human diseases.

RNA modifications In addition to four naturally occurring nucleotides, A, C, G, and U, 96 modified nucleotides have been discovered in RNAs. These modified nucleotides are important for proper biological functions of these RNAs and their modifications are carried out by RNA modification enzymes. It was estimated that 8% of E. coli genes are devoted to RNA modifications. Several important RNA modification enzymes are the focus of our study.

RNA cleavages It is well known that proper RNA cleavage is important in biology (for example, maturation of rRNA and tRNA, splicing of mRNA, and even the production of siRNA involved in RNAi). Less well known is the fact that certain protein toxins from bacteria exert their lethal effect of killing the targeting cell by cleaving certain RNAs in the targeting cell sequence specifically. We are interested in studying a few of such toxins, trying to understand the molecular basis of substrate recognition, as well as mechanism of the cleavage.

Design and engineering of small proteins or chemical ligands The current research in this area is design and synthesis of novel new nucleoside analog inhibitors against HIV-RT, made possible by crystal structures of RT-template:primer-dNTP ternary complexes (carried out by the P.I. during his postdoctoral studies). Future research includes design and engineering of small proteins (based on the knowledge gained by studying protein toxins mentioned above) that can cleave a disease-related RNA with particular sequence and structure. We will also carry out design or screening of organic ligands that will disrupt certain RNA-protein interactions, such as the one in telomerase, that may have implications in certain human diseases such as cancer.