Florence Abadie (left) and Will Hannon comprise the SeattleHub Read Team: 'We are definitely working towards our goal (of a recorder mouse) from multiple different angles in parallel.'
“Oftentimes, on a scientific project, you’re building off of what other people have developed. But a lot of this work has never been done before. And, that makes it exciting.”
Excitement is easy to detect in Florence Abadie’s voice, let alone seeing the gleam in her eyes on the Zoom call. As the Director of the Read Team at the Seattle Hub for Synthetic Biology (SeattleHub), she is at the center of what likely is one of the most consequential scientific projects of our time: creating a mouse whose cells record their own histories over time.
The project, which launched in January of 2024 with a five-year, $70 million grant, is a collaboration among the Allen Institute, BBI, the UW, and Biohub.
Abadie and her colleague Will Hannon comprise the Read Team, one of four groups whose members convene daily in an office suite and lab in South Lake Union seeking to accomplish this daunting mission:
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Sense Team led by Hina Iftikhar – Creating sensors that convert cellular events into barcodes that can then be written into DNA.
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Write team led by Molly Gasperini – Engineering and testing genetic sequences and constructs to create permanent records that are stored in sequential order in the DNA tape in a cell’s DNA.
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In Vivo Team led by James Acosta-Clark – Creating mouse models incorporating the technologies developed by the Sense and Write teams to record cellular events in genomic DNA during an organism’s development and growth.
The work is coordinated by Jesse Gray, Ph.D., SeattleHub’s Executive Director of Strategy and Platform, who sees the four teams as “interrelated into a tightly knit cooperative” to fulfill the mission. Moreover, and contrary to what some might think, Gray said that the role of AI in this project is mostly peripheral – for now.
“The technological solutions we seek can’t all be found on the Internet, so until someone succeeds in creating a ChatGPT for biological design — which probably requires a giant many-modal biological data collection exercise — this isn’t an AI project,” Gray said. “We need data on what each gene is actually doing, not what an algorithm thinks it is – or should be – doing, to create the ability of cells to record their histories and forecast their futures.”
The Read Team’s contribution is integral to SeattleHub’s success.
At the center of that contribution is developing open, reproducible, and scalable workflows for both short and long read sequencing data processing and analysis of recording experiments in both human and mouse cell lines, mouse embryonic stem cell cultures, and mouse models. Moreover, from data generated in the lab, she and Hannon track cell lineages and biological signaling events by reading out the identity and sequential order of DNA barcodes marking these events.
The two work closely together.
“Will is an outstanding scientist,” Abadie said. “He and I have complementary skillsets. And, last year, when he was interviewing for the team, he was clearly enthusiastic about SeattleHub. That matters a lot.”
Hannon has more than a decade of experience in biomedical research and computational biology, and completed his Ph.D. in Molecular and Cellular Biology from the University of Washington, while working with Principal Investigator Jesse Bloom, Ph.D., at the Fred Hutchinson Cancer Center.
In contrast, Abadie worked in industry in the Bay Area for three years after her undergraduate studies at the University of California, Berkeley, and then moved to Seattle in 2017 to start her Ph.D. with BBI Scientific Director Jay Shendure. She “fell in love” with genomic technology development and joined SeattleHub in 2024.
Two years into the initiative, how close is SeattleHub to reaching its goal of a recorder mouse?
“We are definitely working towards our goal from multiple different angles in parallel,” Abadie said. “One of the angles we are approaching our goal from is performing large scale pooled screens. These types of screens allow you to test an exhaustibly large set of DNA sequences in a single experiment and assess their function. In one such screen, in collaboration with the Write team, we are testing orthologous sequences for the “tape” component of our DNA Typewriter machinery that we insert recording barcodes into.
”We’re interested in testing if any of these orthologous sequences might be better, or have higher fidelity, or result in a higher editing rate than the tape sequence we are using now. The sequences we identify from that screen will be potential candidates to go into the recorder mouse that we are continually iterating on.”
SeattleHub is an extraordinary endeavor and Abadie credits Shendure with providing the vision – and motivation.
“Jay has a unique ability to look at the field from a distance and both see where the field is going and where the gaps are,” she said. “And he has a crystal clear vision of where he wants our work to go. Without a clear vision, an organization can really stumble, especially when things become challenging and hard. We, at the SeattleHub, are very lucky that our leadership team has a clear vision that guides our daily work. When there is a clear vision, the motivation easily follows.”
