An entire year has elapsed since I first had the opportunity to write for this blog, which I began with an introduction to NOTCH3, the gene at the center of CADASIL. I had intended to continue writing both explorations of the gene and updates on the project’s progress, both tending towards differently themed discussions in the world of research and of disease pathology.
The COVID-19 pandemic changed everything. The University of Washington, the City of Seattle, and Washington State shut down. I had to literally freeze all my work– taking cells growing in the incubator and dunking them into liquid nitrogen to put them–and put everything else in my life on hold.
But the Seattle Flu Study – a respiratory pathogen surveillance program leveraging the academic, medical, and private research power within King County – did the opposite. The study’s molecular diagnostics team had been among the very first to identify a case of community-acquired SARS-CoV-2 in the United States. This case, just north of Seattle, kicked off the public health interventions that have many of us still working from home.
Before getting the opportunity to join development on the NOTCH3 project, I had been part of a clinical PCR (polymerase chain reaction) diagnostic team that had focused on malaria. PCR played a breakthrough role in this case. PCR detects and amplifies fragments of the viral genome in swab samples, making their presence detectable through fluorescent imaging on a machine. Another researcher detected the very first U.S. community-acquired COVID-19 infection at the lab bench right next to mine. In the following weeks, I found myself spending more and more time talking with the team developing that test.
Because of my background in clinical diagnostics, and the impossible-to-ignore nature of a global pandemic, and because my teammates needed my help, I became fully involved in SARS-CoV-2 testing in March of 2020. Demonstrating that we could detect SARS-CoV-2 with high sensitivity and accuracy was ironically one of our easiest tasks; our test was ready to go early in the spring and we launched SCAN, the Seattle Coronavirus Assessment Network on March 23rd, 2020.
Since then, we’ve halved the size of our PCR reaction without a loss in sensitivity, while still providing multiple test reactions for each participant. We changed swab types to make the test more affordable and easier to ship to participants at home. We transitioned away from RNA extraction platforms that suffered reagent shortages to SwabDirect, a protocol that allows us to perform PCR directly on resuspended and heat-treated swabs. For more than a year now, the lab at UW Medicine has been returning the majority of our results in less than 24 hours. 7 days a week.
My team and I have worked nights and weekends, forming a small but dedicated crew performing our routine testing as well as countless bridging studies required for our advancements to be clinically valid. “Sure, I can try that,” has been my response on Friday night, whether it’s been about growing a new batch of cells for our controls or about testing a new workflow before other techs are trained on it.
Automation has become my specialty – setting up liquid handlers that rapidly distribute hundreds of reactions in minutes and helping renovate new lab spaces for an ever-growing team. Finding improvements to our workflow ergonomics to accommodate our higher throughput and reduce strain from repetitive tasks. I’ve trained six people in molecular diagnostic techniques, and I’m very appreciative of that – maintaining a clinical standard of benchwork and documentation is something from which my CADASIL work will certainly benefit.
With the testing team finally evolving into a stable platform after a tumultuous year of rapid growth and supply chain challenges, I can finally able to return to my CADASIL research. While the chemistry of the SARS-CoV-2 test may be much simpler than what I’m developing for NOTCH3, my troubleshooting skills have been honed from working in such a fast-paced environment. Another year of diagnostics has been insightful, amplifying the experience of my research efforts with a different light. I have very much missed the small and precise research tasks that comprise my NOTCH3 project, but the urgency and proximity, the massive throughput, and the earnest teamwork of SCAN have allowed me to grow as a scientist immensely.
I am pleased to have worked with SCAN and to have helped combat this pandemic, but I am also relieved and invigorated to return to my research on CADASIL. Stay tuned for more updates.