Research Summary
Dr. Crook’s lab characterizes and enhances the ability of probiotic yeast (Saccharomyces boulardii) to synthesize therapeutics in the large intestine. The lab has developed the largest toolkit for engineering this strain and has characterized its colonization kinetics in a variety of mouse models. They have recently applied this knowledge to enable S. boulardii to produce the vitamin A precursor β-carotene in the colon, have enhanced its ability to secrete peptides by more than 10-fold via knockout of key proteases, and are currently investigating the ability of S. boulardii to produce peptides that inactivate the toxins of Clostridioides difficile. He has developed methods accelerating high-throughput screening in yeast, including the invention of retrotransposon-mediated continuous directed evolution, and a set of optimized procedures for genome-wide RNA interference screens. He also developed computer design algorithms that enable fine-tuned control of transcription and translation rates for the first time in yeast. The ultimate goal is to develop platform technologies that de-bottleneck genetic engineering and applying them to transform drug delivery.
CGIBD Focus Area(s): Microbiome
Collaborators: Magness
