Sandia National Labs FY20 LDRD Annual Report

FY20 ANNUAL REPORT

Inducing self-destruction of bacterial pathogens. Bacteria have evolved defenses against the viruses that would otherwise prove lethal to them by incorporating the viral DNA into their own genomes. Some of these bacteria cause human infections and are becoming more resistant to antibacterial therapeutics such as antibiotics. In preliminary research, Sandia scientists demonstrated it is possible to cause the bacteria to self-destruct when they have infected human cells by triggering the expression of this latent viral DNA harbored in the bacterial genome. This work draws on existing computational approaches to identify viral DNA within bacterial genomes and has developed a computational pipeline to identify potential genomic targets. It also builds on

and expands Sandia’s experimental molecular biology capabilities. Ultimately, this work could lead to new techniques to counter intracellular and antibiotic-resistant bacterial infections. (PI: Catherine Margaret Mageeney) When bacterial viruses infect bacteria, they have a choice to kill the bacteria or incorporate the viral genome into the bacterial genome. (2) Many pathogens contain at least one of these viruses. When the bacteria infect human cells, the incorporated virus can be activated, causing self-destruction of the bacterial pathogen.

Engineering the most abundant soluble protein on earth to support food security. Global demand for high-quality, digestible protein as a food source is expected to substantially outpace population growth over the coming decades, necessitating gains in feed-to-food conversion efficiency for sustainable food security. Toward these ends, identifying and producing new protein feedstocks that supplement existing agriculture will be of major importance and have significant impacts that intersect with energy and water infrastructure. Ribulose bisphosphate carboxylase/ oxygenase (RuBisCO) is the most abundant soluble protein on Earth, produced by photosynthetic organisms such as plants, algae, and cyanobacteria, but is not optimal as a food source because it lacks sufficient amounts of methionine and lysine, which are its first nutritionally limiting amino acids. Sandia’s research team genetically engineered a cyanobacterium to significantly increase the amount of these two amino acids in the RuBisCO it produces. This opens the door to use the

modified RuBisCO as feed in agricultural and maricultural applications. Sandia is developing commercial partnerships to exploit this advance. (PI: Ryan Davis)

Schematic for bioengineering of RuBisCO, the most abundant soluble protein, for use as a complete, low- carbon protein source from biomass.

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LABORATORY DIRECTED RESEARCH & DEVELOPMENT