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Rob Knight, UCSD – Pivoting microbiome research and resources to address the COVID-19 pandemic

Prof. Rob Knight, University of California San Diego, was awarded the CRC 1182’s Karl August Möbius Fellowship and visited Kiel University in September 2022. During the award ceremony, we recorded Knight’s lecture on “Pivoting microbiome research and resources to address the COVID-19 pandemic”.

Rapid improvements in high-throughput sequencing, coupled to advances in algorithms, have decreased the cost of microbiome analyses by many orders of magnitude over the past 15 years. The availability of much higher throughput analyses opens up many possibilities: studies spanning the whole body such as the Human Microbiome Project; large-scale cohort studies such as the American Gut Project, the Southern China Microbiome Project, and FINRISK; efforts to characterize the diversity of microbiomes across our planet such as the Earth Microbiome Project; and spatial mapping on scales ranging from an individual person’s diseased lung to a room, a watershed, or even a continent. The COVID-19 pandemic posed a unique challenge to our society but also a unique opportunity to pivot these technologies to study and monitor the genome of this new pathogenic threat. However, many challenges needed to be overcome, such as switching techniques from reading RNA to DNA (SARS-CoV-2 does not have a DNA genome), understanding which assays could run in a clinical versus a research setting and interact with clinical records, and optimizing protocols for high throughput to run thousands of assays per day in a restricted lab space. At UC San Diego, we set up a wastewater monitoring system covering over 300 buildings on campus using ~140 robotic samplers, coupled to a high-capacity clinical COVID-19 testing lab, and used this system for early detection via wastewater of 85% of the cases on campus. Sequencing all the clinical and wastewater positives, including new algorithms to deconvolute the mixture of strains in wastewater sampling, allowed us to relate the clinical and wastewater signal at both the campus and whole-city level, revealing that wastewater is a sensitive advanced warning not only of total SARS-CoV-2 signal but also of the entry and exit of individual variants from the population. In turn, the advances made in responses to the pandemic have yielded efficiencies of scale and improved methods for concentrating and extracting relevant RNA, which will be generally useful for microbiome research as well as for responding to the next pandemic.

More on Rob Knight’s work: