Saurja DasGupta

RNA plays a crucial role in biology and its significance continues to grow as new discoveries are made. The DasGupta lab will focus on a holistic exploration of RNA. We will investigate RNA structure, function, and evolution. By studying its structure, we will explore how its three-dimensional shape influences its function and its interactions with other biomolecules. We are deeply interested in a special class of RNA molecules that show catalytic activity, called Ribozymes. We will use biochemistry, high-throughput sequencing, and structural biology approaches to understand how this special class of RNA molecules catalyze chemical reactions when most RNAs do not. We are also interested in the evolutionary processes that allow RNA molecules to adapt to new functions like enzyme catalysis or ligand binding (as in aptamers). We will routinely use combinatorial techniques like in vitro selection and directed evolution to discover RNAs de novo that perform functions not found in biology.

In addition to its many biological roles, RNA bears a profound weight of biological history. It is widely accepted that the earliest forms of life on Earth (~3.8 bya) used RNA to constitute their genomes and as enzymes. Understanding the capabilities of RNA is thus crucial for unraveling the mysteries surrounding life's origins and advancing our knowledge of early evolutionary processes. The DasGupta lab aims to create synthetic models of the earliest cells that show life-life behaviors such as growth, division, competition, and ultimately Darwinian evolution to understand how life emerged from non-living matter. These studies will reveal fundamental physical and chemical principles underlying biology. We are also invested in using evolutionary approaches to develop RNA-based technologies to probe largely unexplored areas of RNA biology. This includes generating reagents to interrogate the biologies of RNA cleavage and non-canonical RNA capping, and generating aptamer-based biosensors.

Publications

1. "Crystal structure of the Varkud satellite ribozyme” Suslov, N.B.; DasGupta, S.; Huang, H; Fuller, J.R.; Lilley, D.M.J.; Rice, P.A.; Piccirilli, J.A. Nat. Chem. Biol. 2015, 11, 840-846.
2. “Structural Basis for substrate helix remodeling and cleavage loop activation in the Varkud Satellite ribozyme" DasGupta, S.; Suslov, N.B.; Piccirilli, J.A. J. Am. Chem. Soc., 2017, 139, 9591-9597.  
3. "RNA-catalyzed RNA ligation within prebiotically-plausible model protocells” DasGupta, S.; Zhang, S.; Smella, M.P.; Szostak, J.W. Chem. Eur. J., 2023, e202301376.
4. "Structural basis for substrate recognition and catalytic activity of a self-alkylating ribozyme" Krochmal, D.; Shao, Y.; Li, N-S.; DasGupta, S.; Shelke, S.A.; Koirala, D.; Piccirilli, J.A. Nat. Chem. Biol., 2022 doi: 10.1038/s41589-021-00950-z