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Image two hands representing connection of RNA between Chemistry and Biology

MCB RNA Faculty Candidate Seminar: Dr. Saurja DasGupta (Harvard Medical School), "RNA: Catalyzing Life’s Origins"

Event Type
The School of Molecular and Cellular Biology (HOST: Dr. Auinash Kalsotra, Biochemistry)
Charles G. Miller Auditorium, B102 Chemical and Life Sciences Laboratory
Mar 6, 2023   2:00 pm  
Dr. Saurja DasGupta
Cara Day
Originating Calendar
Biochemistry Department Seminars

*** NOTE: Time & Date is Monday, March 6 from 2:00-3:00 PM ***

ABSTRACT:  Life originated about 4 billion years ago via a series of steps involving a gradual increase in molecular and organizational complexity. It is widely accepted that the earliest lifeforms likely used RNA to constitute their genomes and as enzymes (ribozymes). Ribozymes were central to the success of primordial life in this ‘RNA World’. Therefore, to understand RNA-based primordial life, we must understand how ribozymes function, how they acquire new functions through evolutionary adaptation, and how such complex RNA molecules may emerge in a world without proteins.

First, I will discuss how specific structural features allow ribozymes to perform the various steps of enzymes catalysis. For this, I will use crystal structures of the Neurospora VS ribozyme, an enzyme that catalyzes site-specific RNA cleavage. Next, I will outline our efforts to reconstruct pathways, consistent with the constraints of early earth, that would allow cell-like systems to emerge from simpler components. We used evolutionary approaches to identify ribozymes that catalyze RNA assembly using short oligonucleotide building blocks as substrates. We also used synthetic approaches to outline pathways that allow these ribozymes to emerge through the enzyme-free assembly of RNA building blocks.

To model the emergence of compartmentalized catalysis – a hallmark of biology – we demonstrated ribozyme-catalyzed RNA assembly within models of primordial cells (protocells) bounded by prebiotically relevant fatty acid membranes. This result represents a step toward the replication of primordial genomes within self-replicating protocells. Collectively, our efforts to integrate various aspects of primordial RNA assembly have brought us closer to building a selfreplicating chemical system with the potential to evolve spontaneously.

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