Engineering topics
Damoiseaux, Robert
Publications and source records attributed to Damoiseaux, Robert.
Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils
The self-assembly of the Nucleocapsid protein (NCAP) of SARS-CoV-2 is crucial for its function. Computational analysis of the amino acid sequence of NCAP reveals low-complexity domains (LCDs) akin to LCDs in other proteins known to self-assemble as phase separation droplets and amyloid fibrils. Previous reports have described NCAP’s propensity to phase-separate. Here we show that the central LCD of NCAP is capable of both, phase separation and amyloid formation. Within this central LCD we identified three adhesive segments and determined the atomic structure of the fibrils formed by each. Those structures guided the design of G12, a peptide that interferes with the self-assembly of NCAP and demonstrates antiviral activity in SARS-CoV-2 infected cells. Our work, therefore, demonstrates the amyloid form of the central LCD of NCAP and suggests that amyloidogenic segments of NCAP could be targeted for drug development.
Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors within Nucleotide M
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Development of Arrayed CRISPR-based Libraries for Functional Genomics Screening
Sandia National Laboratories and The Regents of the University of California, on Behalf of its Los Angeles Campus will collaboratively engage in the development of arrayed formatted genomic screening libraries based on CRISPR genome-editing technology. The effort will create libraries intended for use by the scientific community in research that includes therapeutic target discovery and comprehensive pathogen-host interaction analysis of agents of national security interest.
Arrayed Guide RNA Libraries for CRISPR-based Gene Knockout Screening
collaboration to develop arrayed formatted genomic screening libraries based on recently developed genome-editing technology termed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR-based screening allows for potent knockout of cellular genes with a genome-wide level scalability. With the development of CRISPR knockout libraries, comprehensive analysis of pathogen-host interaction and therapeutic target discovery can be performed against pathogens of biothreat concern and national security interest. Under this work, a CRISPR knockout screen was executed against the mosquito-borne pathogens Zika virus and Rift Valley fever virus. We identified existing as well as novel host genes involved in infection by these viruses. By discovering host genes essential for infection, we can design anti-viral treatments using those identified gene or gene products as targets. The scope of this partnership was within Sandia’s mission area and national security of reducing biological dangers from emerging infections or biodefense threats.