The Ferré-D'Amaré group is broadly interested in elucidating the physical and chemical underpinnings for the biological functions of RNA, and in applying the resulting insights to the development of molecular and pharmacological interventions in health and disease states.
1. Catalytic RNAs
Ribozymes are non-coding RNAs that can precisely position reactants and accelerate chemical reactions by preferentially stabilizing their transition states. Some fundamental biological processes (such as translation, splicing and tRNA maturation) are universally catalyzed by ribozymes. Several ribozymes are also known to play key roles in the replications and virulence of important human pathogens.
2. Gene-regulatory RNAs
Our group has made numerous breakthroughs in the study of riboswitches, which are non-coding mRNA domains that regulate gene expression in response to the intracellular concentration of their cognate ligands. Depending on the riboswitch, ligands range from simple ions and metabolites to second messengers to other RNA molecules. Many riboswitches control virulence of bacteria, and therefore are attractive targets for novel antibacterials.
3. New tools for RNA cell biology
Tens of thousands of non-coding RNAs have been discovered in the human transcriptome, and new tools for studying them in live cells are urgently needed. Fluorescent RNAs offer the prospect of revolutionizing the study of RNA in the same way that green fluorescent protein (GFP) and its homologs transformed the study of proteins. Through structure-guided engineering and optimization of fluorescent RNAs, we develop new tools for the analysis of expression, turnover, trafficking and localization of non-coding RNAs.