Current Research and Scholarly Interests
Our lab strives to predict and design how biopolymer sequences define and regulate biopolymer structure/function, focusing on medically important RNA and RNA/protein complexes.
We develop algorithms to predict the structures and energetics of RNAs and RNA/protein interfaces at high resolution, with an increasing focus on ribosomes and viruses. We test these ideas through community-wide blind trials and by solving molecule structures and structure ensembles with chemical mapping, NMR, crystallographic, and cryoelectron microscopy data. Notable achievements include top models in the majority of RNA-Puzzles blind structure prediction challenges and first experimental structures of several historically and biomedically important RNA molecules, such as the Tetrahymena ribozyme.
Complementary to this computational research, we are developing information-rich biochemical methods to model the myriad structures of non-coding RNAs that remain unknown. Current efforts focus on probing the extent and biological impact of RNA structure and conformational change in fundamental processes like splicing and mRNA transport in brain cells and viruses.
In addition to modeling RNAs, we aim to design new ones for basic science, diagnostics, therapeutics, and vaccines. Our videogame project Eterna seeks missing rules and novel molecules for medicine by giving citizen scientists access to high-throughput wet-lab experiments. Notable achievements include the first algorithm for automated 3D RNA design, development of the current community benchmark for RNA design, discovery of optimal 'zero-energy' switches made of RNA, and invention of RNA calculators for point-of-care diagnostics responsive to complex gene signatures for active tuberculosis. This project has also given rise to several firsts in citizen science, including the first papers written by videogame players as lead authors and as sole authors.
