Michael T. Laub

Jan 7, 2025 | biorxiv.org | Peter DeWeirdt |Emily Mahoney |Michael T. Laub

AbstractAnti-phage defense systems protect bacteria from viruses. Studying defense systems has begun to reveal the evolutionary roots of eukaryotic innate immunity and produced important biotechnologies such as CRISPR-Cas9. Dozens of new systems have been discovered by looking for systems that co-localize in genomes, but this approach cannot identify systems outside defense islands.

Feb 21, 2024 | nature.com | David Ding |Nathan Rollins |Noam Prywes |David Savage |Michael T. Laub

AbstractRecent developments in protein design rely on large neural networks with up to 100s of millions of parameters, yet it is unclear which residue dependencies are critical for determining protein function. Here, we show that amino acid preferences at individual residues—without accounting for mutation interactions—explain much and sometimes virtually all of the combinatorial mutation effects across 8 datasets (R2 ~ 78-98%).

Nov 8, 2023 | nature.com | Michael T. Laub

AbstractCellular novelty can emerge when non-functional loci become functional genes in a process termed de novo gene birth. But how proteins with random amino acid sequences beneficially integrate into existing cellular pathways remains poorly understood. We screened ~108 genes, generated from random nucleotide sequences and devoid of homology to natural genes, for their ability to rescue growth arrest of Escherichia coli cells producing the ribonuclease toxin MazF.