My research group aims to understand how ion channels and transporters function at the atomic level through the use of structure biology and electrophysiology. Specifically, we seek to elucidate the basic principles of channel regulation and ion selectivity among tetrameric cation channels, the largest ion channel family whose functions are central to nerve excitation, muscle … Continued
The overarching goal of my lab is to understand the fundamental behavior of RNA and proteins and, in turn, how these behaviors determine and impact biology more broadly. We are particularly interested in questions of how enzymes work, how RNA folds, how proteins recognize RNA, and the roles of RNA/protein interactions in regulation and control, … Continued
My lab focuses on how the ribosome coordinates the complex molecular event of translation and its regulation. Many projects rely on biochemical methods that use in vitro translation systems fully reconstituted from both bacterial and yeast components. Most projects in our lab also incorporate ribosome profiling and other high throughput genome-wide approaches to connect biochemical … Continued
Research in our laboratory focuses on understanding the relationship between the structure of medically-relevant biological catalysts and the biological function. Currently, the main focus is investigation of the mechanism, molecular recognition, regulation, biological substrates and biological function of enzymes that catalyze post-translational modifications, including protein farnesyltransferase, protein geranylgeranyl transferase, and histone deacetylases. These enzymes are … Continued
My lab is researching the molecular basis for CRISPR-Cas genome protection and editing. CRISPR is a surgical tool for changing the code of life. In bacteria, CRISPR systems preserve invading genetic material and incorporate it into surveillance complexes to achieve adaptive immunity. Crystal structures of diverse Cas9 proteins reveal RNA-mediated conformational activation. Further, my group … Continued
My laboratory is conducting research on the advanced functions of nucleic acids. Some of the most fundamental processes in all domains of life, such as genetic information storage and the biosynthesis of proteins, intimately rely on the special functions of DNA and RNA molecules. Some of these tasks require that nucleic acid polymers simply code … Continued
When a virus infects an animal cell, including a human cell, double-stranded RNA (dsRNA) matching viral sequence is found in the cell. Viral dsRNA is recognized as foreign and an immune response is mounted. Viruses were once thought to be the sole source of long dsRNA, but our laboratory has identified numerous long dsRNAs that … Continued
Our work focuses on energy coupling, assembly mechanics, and biological regulation of molecular machines using a combination of hybrid structural, bulk biochemical, and single-molecule methods. We have a long-standing interest in understanding how type II topoisomerases are inhibited by anti-cancer and antibacterial agents, how resistance to topoisomerase poisons impacts enzyme function, and how topoisomerase-DNA cleavage … Continued
Our lab works on a range of projects related to the control of pre-mRNA splicing and its role in gene regulation. We study the mechanisms of action of splicing regulators, as well as how these proteins affect biological processes such as neuronal development, tumor progression, and the inflammatory response. Long-standing projects have examined two families … Continued
Our development of algorithms for molecular modeling of protein structure is at the center of Rosetta, a powerful discovery engine that has largely cracked the “protein folding code”. My group was the first to accurately produce a fully de novo designed protein, “Top7”. We then designed an enzyme to perform the Diels-Alder reaction, a reaction … Continued