Time may be a construct, but it’s not without consequence. That’s especially true when it comes to cells, which accumulate genetic changes over their lifespan that can ultimately lead to disease.
Yet despite knowing this, scientists currently can only see the final outcome of the ravages of time on cells—not how things go awry along the way. Now, a collaboration between the Allen Institute, the Chan Zuckerberg Initiative and the University of Washington aims to change that. Dubbed the Seattle Hub for Synthetic Biology, the enterprise will build new technologies that let scientists measure changes in single cells in real time, with the goal of using the tech to research, diagnose and treat disease.
In a press release about the development, Jay Shendure, M.D., Ph.D.—a geneticist and the hub’s new director—likened the tech the initiative aims to build to a “genomic smartwatch.”
“Currently … we’re limited to either observing how a few things change over time with a microscope, or measuring everything but only at the moment in time that we break open the cell,” Shendure said in the release. “With the kind of genomic smartwatch that we’re aiming to build, one could recover the full autobiography of each cell, rather than only the last page.”
Advances like single-cell multi-omics technologies have made it possible to measure multiple dimensions of individual cells all at once, such as gene and protein expression, metabolism and more. But while these tools have improved scientists’ understanding of cell behavior and biology, including in the context of tumor immunology, they’re still just a snapshot in time. The tools built at the Seattle Hub for Synthetic Biology will give scientists a way to record changes in cells as they happen, which can ultimately help them “not just observe, but actively intervene to treat disease in real time,” as the hub put it on its website.
Shendure has been conducting research in this realm already through his lab at the University of Washington School of Medicine, which collaborates with labs at Caltech and the University of Basel in Switzerland to form the Allen Discovery Center for Cell Lineage Tracing. The lab’s work spawned tech like the DNA Typewriter, a tool that can be paired with single-cell RNA sequencing to changes in DNA to reconstruct the lineage of generations of cells. They have also developed a technique called enhancer-driven genomic recording of transcriptional Activity in multiplex or ENGRAM, which records the activity of DNA sequences called enhancers to trace the order in which different genes are activated.
ENGRAM and the DNA Typewriter will both be at the heart of the hub’s research, its website said. The work also won’t be limited to following the trajectory of one cell at a time, but millions of them all at once at the scale of entire organisms. This way, the researchers will be able to understand how changes to genes and the environment give rise to changes in cells and therefore tissues, with the outcome of driving disease.
“By developing new technologies to measure and understand the history of our cells over time, including how they are impacted by the environment around them, genetic mutations and other factors, we can expand scientists’ understanding of what happens at the cellular level when we go from healthy to sick and help pinpoint the earliest causes of disease,” Priscilla Chan, M.D., co-founder and co-chief executive officer of the Chan Zuckerberg Institute, said in the press release.