Researchers opened the doors Monday to the new Seattle Hub for Synthetic Biology, a collaboration between the Allen Institute, the Chan Zuckerberg Initiative and the University of Washington.
The hub combines “academic creativity with startup-style industrial execution,” said Jesse Gray, senior director of scientific operations and strategy, who was previously head of discovery at gene editing startup Ascidian Therapeutics.
The hub’s first main goal is to build a “biological recorder mouse,” enabling researchers to track biological actions such as cell divisions and molecular signaling in a live mouse across time.
Monday’s tour took place at the hub’s labs at Dexter Yard, a life sciences development in the South Lake Union neighborhood across from the Allen Institute, which is contributing $35 million to the hub over the next five years.
The Chan Zuckerberg Initiative is providing the same amount, and the UW is a source of foundational technology for the new hub.
The initiative leverages DNA-based technology developed in the lab of the hub’s lead scientific director Jay Shendure, a UW professor of genome sciences. During the tour, he called the approach a “symbolic language for longitudinally recording biology over time.”
The method involves generating DNA barcodes for each cell that reflect biological activity. Scientists place a DNA “tape” inside a founder or stem cell. The DNA tape is edited through generations of cell division, with each edit occurring in sequential order along the tape — generating a readout of the timing of cellular events.
Shendure and his colleagues introduced this “DNA typewriter” technique in a 2022 study published in Nature. There, they used the method to reconstruct a cell lineage tree, tracing how a single cell multiplied into thousands of cells. More recently, his lab adapted the technique to record the long-term activity of cell signals.
Ultimately, the researchers think the methods can be used to trace an even broader variety of cellular states and actions, such as metabolic status, cell-cell contact, and neuronal signaling.
The approach is “foundational technology” said Stephen Quake, head of science at the Chan Zuckerberg Initiative, during a fireside chat at the Allen Institute. New drugs and treatment should ultimately result from the research, he said.
Potential applications include assessing the actions of therapeutic cells and improving their design. Another application might be to track body-wide how a mouse responds over time to specific drugs or other perturbations.
Marion Pepper, professor and chair of Immunology at the UW, is excited to explore potential uses in immunotherapy.
“Having these types of tools and technological developments applied to immune cells will revolutionize how we treat disease,” said Pepper, who co-directs the hub with UW associate professor of genome sciences Cole Trapnell. “We’re going to learn so much about these cells that we’ve never been able to visualize or understand,” added Pepper.
The Seattle Hub for Synthetic Biology, first announced in December, now has 15 staff members and plans to hire up to a dozen more by the end of next year, and around 50 within five years.
Shendure sees an opportunity to snap up talent with industry experience and the ability to spot commercial opportunities. At the same time, both the Allen Institute and the Chan Zuckerberg Initiative have a commitment to open science — a culture that has also eased their collaboration, said hub leaders.
Typewriter teams
The Seattle Hub for Synthetic Biology currently occupies 3,600 square feet in Dexter Yard, and will expand to 12,000 square feet in 2025. During the tour, visitors were introduced to four research stations.
- The Sense Team develops sensors to detect events in cells and translate the information into records that can then be written into DNA. A key aim is that “editing events correspond to the intensity and direction of signals,” said team leader Hina Iftikhar, who was previously a senior scientist at Seattle cell therapy company Sana Biotechnology.
- The Write Team develops the technology for recording to DNA. The information is recorded by the “DNA typewriter” as insertional edits. One aim is to make sure the bar codes are stable and accurate, said team member Emily Cliff.
- The Build Team is establishing what team leader Sudarshan Pinglay calls a “DNA Atelier” or studio. These researchers will generate very large DNA molecules, consisting of hundreds of thousands of base pairs, to engineer into cells.
- The Read Team interprets the edited DNA sequence readouts from the DNA Typewriter, yielding a record of changes occurring in cells over time. The team uses computational approaches and artificial intelligence to model cells and provide feedback to the other teams on how to improve the technology, said team leader Florence Chardon.
