Molly Gasperini (front) and the Write Team of the the Seattle Hub for Synthetic Biology: Middle Row (left to right) Yasuhiro Kyono, Grace Travis, and Shuhua Luo; (back row (left to right) Hannah Starkey, Shruthi Vijay Kumar, and Emily Cliff.
“I absolutely fell in love lab work. You spend time coming up with ideas, discussing them with peers, and you get to do more experiments with your own hands, and then you analyze the results together. What a privilege!” Molly Gasperini, Ph.D.
Gasperini was referring to her work as a research assistant 15-plus years ago in the lab of UW Medicine’s Mary-Claire King, but she might as well have been discussing her current role with the Seattle Hub for Synthetic Biology (SeattleHub). She serves as the lead scientist for the Write Team, a group charged with developing CRISPR-based tools that engineer cells to record their histories to their own genome.
For many, this might appear to be a daunting challenge. For Gasperini and her team of six researchers it is an exciting opportunity of cutting-edge of biology and technology.
“I am so lucky to work with this team,” said Gasperini, who joined SeattleHub in July of 2024 as Associate Director of Genome Engineering, following a 10-month stint at the Allen Institute. “The team members are really smart and so fun to work with. We get to work on tricky problems and tackle these problems in different ways together.”
Tackling tricky problems is one way to describe the mission the Write Team members – and all the other SeattleHub researchers – are on together: tracking and recording entire living histories of individual cells.
The day-to-day work to accomplish the mission is divided among four teams. In addition to the Write Team, they are:
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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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Read Team led by Florence Abadie – Developing computational pipelines and methods to analyze sequencing data and to characterize lineage relationships and biological signaling between cells across various tissues.
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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.
For Jesse Gray, Ph.D., SeattleHub’s Senior Director of Strategy and Operations, the endeavor sits at a fulcrum between two eras of biology.
“SeaHub is fantastically exciting,” he said. “As biologists, we’re still very much transitioning from understanding biology to engineering it. It’s now becoming more about bending biology to our will and trying to make it do things. Here, we’re wrangling biology and tackling all the puzzles required to make it work.”
“Wrangling” and “tackling puzzles” are appropriate descriptions for the Write Team’s work.
Those CRISPR-based tools the team develops to record cellular histories can include a wide range of data, including information on cellular lineages, internal occurrences and decisions, external signals or stressors, phenotypic changes, and, in theory, any biological signal. It is essential, Gasperini said, that this information is recorded sequentially.
To accomplish this, team members use DNA Typewriter. A synthetic DNA sequence, called a Tape, is installed into a cell’s genomic DNA. The first segment of Tape is nicked using a CRISPR-Cas9 enzyme. A short DNA sequence, known as a molecular barcode, is then inserted into the cut site. The barcodes function similar to the Morse Code, where each unique barcode translates to a specific cellular event.
Thus, the insertion of the barcode into the DNA creates a record of a specific event.
“While our work may be easy to describe, it is filled with complications,” said Gasperini. “You have to adapt the cell’s native DNA repair machinery to our purposes, you need to optimize which CRISPR enzyme tool to use to make sure it is working accurately, and, of course, you need to make sure your work does not kill the animal. There’s a whole host of genome engineering issues and CRISPR technology challenges that come about from relying on that method to make the permanent record.”
Much of the Team’s time in 2025 was devoted to trial and error, followed by new insights, followed by more trial and error and more new insights, all the time building knowledge by refining ideas and theories based on evidence – the essence of the scientific process. This year, by growing new mice and testing those CRISPR-based recording tools, Gasperini and her colleagues hope for significant progress toward fulfilling Seattle Hub’s mission.
But Gasperini is as much realistic as she is hopeful.
“All the design efforts, all the experiments, it’s all hopes and dreams until you see that data,” she said. “It’s almost like gambling and it can be addicting when you get that breakthrough. This represents the grounding excitement with Seattle Hub and all the other jobs I’ve had.”
