NEW YORK – The Allen Institute and the Chan Zuckerberg Initiative have each committed up to $35 million over five years to fund a new synthetic biology research center in partnership with the University of Washington.
UW researchers Jay Shendure, Marion Pepper, Cole Trapnell, and Jesse Gray will lead the Seattle Hub for Synthetic Biology, announced earlier this month, as it builds on CRISPR-based technology for cell tracing and using genomes as biological recorders.
"Imagine being able to put a smart watch into each of your cells to record the genome itself and everything that cell is experiencing," Shendure said in a statement. "Currently, when biologists take measurements, we're limited to either observing how a few things change over time with a microscope or to measuring everything but only at the moment in time that we break open the cell. With the kind of genomic smart watch that we're aiming to build, one could recover the full autobiography of each cell, rather than only the last page."
The project will build on two core technologies, both developed in Shendure's lab: DNA Typewriter and ENGRAM.
DNA Typewriter, published in 2022, offers the ability to do in vivo molecular recording. It uses ENGRAM (ENhancer-driven Genomic Recording of transcriptional Activity in Multiplex), a prime editing system where biological signals are coupled to the production of guide RNAs to insert a sequence into a stretch of genome of otherwise inactive CRISPR target sites.
Researchers at the hub will look to advance the use of CRISPR-based genome editing as a cellular historian, a concept that Shendure has been pursuing since at least 2016. His lab was one of several to publish papers at that time, showing the ability to record information in DNA using CRISPR. Shendure and Alexander Schier, who was then at Harvard, published a method called Genome Editing of Synthetic Target Arrays for Lineage Tracing (GESTALT), which they used for cell lineage tracing. Around the same time, Timothy Lu of MIT suggested using CRISPR as a memory device for cellular events, and George Church's Harvard lab — where Shendure was once a graduate student — also described a technology that could be used for lineage tracing and molecular recording.
In addition to DNA Typewriter and ENGRAM, the Seattle Hub will develop complementary technologies, such as large-scale DNA synthesis and genomic landing pads, Shendure said in an email. In addition, the hub will seek to characterize the function of genes in vivo. "In both cases, the objective is to connect molecular details to time and, ultimately, better understanding of functional circuits and genes," he said.
Early work will focus on organism development and immunology. "The immune system impacts virtually every area of human health, so a deeper understanding of how genes lead to changes in health and disease has the potential for widespread impact," Shendure said.
"Both development and immunology have outstanding in vitro and in vivo models on which we can rapidly iterate for technology development, and they are both complex, temporally dynamic systems in which longstanding questions have been unaddressable by conventional measurement paradigms."
The researchers said that the Seattle Hub would operate with a commitment to "open science" and would share their findings. Specifically, they plan to publish preprints, adhere to FAIR data principles, and release data, tools, and methods to the community. "We already follow open science practices in our own work and will be extending those practices to the new hub," the Seattle Hub leadership team said in an email.
Whether that will extend to open licensing practices for any technologies developed at the Hub is unclear. Shendure has applied for a patent for a "Multiplex, temporally resolved molecular signal recorder and related methods" based on the two technologies.
The Hub will move into lab space at the Dexter Yard in Seattle's South Lake Union area.