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‘A Primordial RNA Alphabet’: Nobel laureate discusses the origin of life at annual Weissman Lecture
Nobel Laureate and University of Chicago professor Jack Szostak delivered two lectures on the origin of life to an audience of professors, graduate, and undergraduate students the Monday and Tuesday before Spring Break.
The event, titled “A Primordial RNA Alphabet,” was organized by WashU’s Department of Chemistry as part of its annual Samuel I. Weissman Lecture. Since its establishment in 2011 to honor the late Professor Samuel Weissman, researchers from across the world have discussed topics ranging from dark matter to cell imaging in previous lectures.
The topic this year was ribonucleic acid, or RNA — a single-stranded molecule (not to be confused with the double-stranded DNA) that many scientists now believe was the first molecule capable of self-replication.
In 2009, Szostak, along with two other researchers, was awarded the Nobel Prize in Physiology or Medicine for his work on how chromosomes are protected during crucial biological processes. Since then, Szostak has turned his attention to RNA and developing viable models to explain the key processes that likely occurred almost 4 billion years ago, well before the first evidence of life entered the fossil record.
During his talk, he discussed his research into how RNA strands (also known as “primers”) can extend themselves using only simple chemical reactions and readily-available molecules — allowing them to grow and replicate in conditions likely present in the early Earth’s atmosphere.
Towards the end of his lecture, Szostak also highlighted the importance of not limiting the research to just RNA itself.
“Everything we know is focused toward RNA. … I feel very disturbed if we only know about one thing,” he said.
When asked whether he thought alternative pathways to self-replication could exist, Szostak said it would be fascinating to design and synthesize other genetic materials, then test each of them to explore alternate pathways of life formation on Earth. However, he also noted that it can be very difficult to see how they would emerge under early Earth conditions.
“These are all great ideas,” he added, “but in experimenting with them you might find that none of them really work.”
During his second lecture on Tuesday, Szostak went into more detail about the experimental results and difficulties his lab has encountered.
These included different aspects of the RNA replication process and the drawbacks that might be associated with them. He discussed potential metal catalysts, the 2-aminoimidazole group — an intermediate in the RNA replication process — and template copying biases, which occur when certain nucleotides are favored over others during primer extension.
“[Problems with biases in RNA template-copying] first emerged in the 1980s,” he said. “We had no idea how to deal with these problems for a long time.”
Szostak then explained deep sequencing, which allowed his lab to measure gene expression and identify changes in RNA structure, before finishing his talk on a discussion of the circular viral genome model. Since some viruses rely heavily on RNA, he hopes to use this model to ultimately shed more light on the self-replication process.
“Hopefully in the next couple of years, we’d be able to put together a copying chemistry process … and see replication happen for the first time,” he concluded, to warm applause.
Chair of WashU’s Department of Chemistry and professor Jennifer Heemstra later expressed the importance of events like Szostak’s talks.
“The Weissman lecture series is an outstanding opportunity to celebrate both the history and the future of chemistry at WashU,” she wrote in an email to Student Life. “We are fortunate for the opportunity to have a leader in our scientific field visit us each year for the Weissman lecture series and present their work both to specialists in the field and to the broader WashU community.”
Heemstra also expressed that the topics Szostak highlighted are central to understanding life’s origins on all levels.
“His lectures offered exciting chemical insights into these replication reactions while also contextualizing the work in the larger field,” she wrote. “He inspired us to instead think more creatively and be open to alternative mechanisms that we might not have previously considered.”