Nucleic Acids: Catalysis, Recognition and Role in Biosynthesis

The chemical basis of nucleic acid structure and function is the second major research theme in Yale’s Chemical Biology Graduate Studies. While nucleic acids often serve as the information storage and transfer molecules for living organisms, they also participate in a broad variety of other cellular functions. These include amino acid biosynthesis, protein localization, transcriptional control, and translation. Possibly the most dramatic example of an alternative function for a nucleic acid is the role that RNA plays as a biocatalyst, including RNA molecules that participate in RNA processing and protein synthesis. The chemical interactions that facilitate these biological functions provide a wealth of new research opportunities for graduate students seeking training at the interface of chemistry and biology. Many of these projects are multidisciplinary and will involve training and scientific guidance from teams of faculty advisors that cross traditional boundaries form cellular biology to synthetic organic chemistry. This program of study requires a broad scientific knowledge that is founded in chemical mechanism, but motivated by biology function. Students and faculty from these four groups meet once a month that the interdepartmental RNA group meetings to get input on the projects and to sharer scientific results.

There are three research advisors in the training program that emphasize the chemical biology of nucleic acids:

Ronald Breaker (MCDB) also studies catalytic nucleic acids. His lab develops RNA “molecular switches” whose functions can be controlled by small organic molecules.

Caitlin Davis (Chemistry) studies protein-RNA interactions and biomolecular assemblies in living cells and organisms.

Farren Isaacs (MCDB) is recoding genomes of microorganisms to maximize biosynthetic pathways involved in natural product syntheses.

Chenxiang Lin (Cell Biology, Nanobiology) synthesizes and engineers DNA nanostructure-based molecular tools to support diverse biological studies.

Anna Pyle (MCDB) studies the structure and function of RNA and molecular motor proteins that interact with RNA, including associated small molecule drug development.

Matthew Simon (MBB) studies chromatin and large non-coding RNAs (1ncRNAs).  Many of the projects in his lab include technology development, and use approaches from protein engineering, synthetic chemistry, nucleoside biochemistry, molecular biology and genomics to investigate the molecules that regulate our genomes.

Scott Strobel (MB&B) investigates the chemical basis of nucleic acid biological functions including RNA catalysis, RNA modification and RNA cytoplasmic localization.