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This seminar from the Broad-MIT Seminar Series in Chemical Biology features Phil Holliger from MRC Laboratory of Molecular Biology discussing "Replicating RNA with RNA." Explore the critical event in the origin of life - the emergence of self-replicating RNA molecules capable of mutation and evolution. Learn how modern RNA enzymes (ribozymes) generated through in vitro evolution allow scientists to study RNA-catalyzed RNA replication. Discover the evolution of RNA polymerase ribozymes (RPRs) that can synthesize other ribozymes and RNA oligomers, with their activity enhanced by simple lysine-rich peptides from ribosomal cores. The talk covers recent engineering breakthroughs in RPRs that use trinucleotide triphosphates as substrates, enabling the copying of highly structured RNA templates and non-canonical replication modes. Understand how a recently discovered small RPR can synthesize its own positive and negative strands - a significant step toward self-replication. The presentation also examines how structured media like water ice's eutectic phase and coupled pH/freeze-thaw cycles can support RPR function and enable multi-cycle replication of double-stranded RNAs.
Syllabus
Broad—MIT Seminar Series in Chemical Biology: Phil Holliger (2025)
Taught by
Broad Institute