Sandia National Labs FY20 LDRD Annual Report

FY20 ANNUAL REPORT

Permafrost resilience bioindicators to improve climate model fidelity. Increasing temperatures in the Arctic are thawing permafrost soils that previously remained frozen. The increased microbiome activity in these soils has been shown to release trapped carbon as potent greenhouse gases, such as methane, but with large degrees of uncertainty. To better understand the role of permafrost biology, this project developed approaches to improve genomic and metabolomic analyses of the permafrost microbiome by enriching metabolically active, dormant, and dead microbes through fractionation and sorting of microbial populations. Researchers developed techniques for high-throughput microbial enrichment, repurposed an existing targeted assembly and annotation pipeline to identify a potential bioindicator of methane production in

permafrost ecosystems, and applied these approaches to permafrost core samples. These analyses will provide data to improve the biological fidelity of permafrost impact on climate models. (PI: Chuck Smallwood) Enhanced genomic and metabolomic analyses on permafrost cores, such as the one shown here, will provide biologically relevant input to climate models.

Engineering cells for personalized antimicrobial therapy. Increasing use of antibacterial and antiviral drugs has led to microbial infections that are resistant to these types of therapies, requiring new approaches. One promising broad-spectrum approach is to enhance the human immune system itself to better deal with pathogens on its own. The Sandia and UC Davis research teams have demonstrated that by applying the gene engineering technique CRISPR to mesenchymal stromal cells (MSC), one type of human stem cell, the specific antimicrobial properties in these cells are enhanced. They also proved that modifying MSC surface protein expression can control their behavior. To characterize the properties in these engineered MSC populations, they established and utilized a novel combination of high-throughput population and single-cell nucleic acid sequencing, mass-spectrometry-based protein expression surveys, and high-throughput imaging capabilities. Although animal and human studies are necessary next steps, the work provides a roadmap for engineering of MSCs for immunomodulation applications. Ultimately, these results can lead to expanded antimicrobial therapies and increase the resilience of our healthcare system to future pandemics. (PI: Raga Krishnakumar)

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LABORATORY DIRECTED RESEARCH & DEVELOPMENT