Many powerful molecular biology tools have their origin in nature, and, often, microbial life. From restriction enzymes to CRISPR-Cas9, microbes utilize a diverse array of systems to get ahead evolutionarily. We are interested in exploring this natural diversity through bioinformatics, biochemical, and molecular work to better understand the fundamental ways in which living organisms sense and respond to their environment and ultimately to harness these systems to improve human health. Building on our demonstration that Cas9 can be repurposed for precision genome editing in mammalian cells, we began looking for novel CRISPR-Cas systems that may have other useful properties. This led to the discovery of several new CRISPR systems, including the CRISPR-Cas13 family that target RNA, rather than DNA. We developed a toolbox for RNA modulation based on Cas13, including methods for precision base editing. We are expanding our biodiscovery efforts to search for new microbial proteins that may be adapted for applications beyond genome and transcriptome modulation, capitalizing on the growing volume of microbial genomic sequences and building on our bioengineering expertise. We are particularly interested in identifying new therapeutic modalities and vehicles for delivering cellular and molecular cargo. We hope that this combination of tools and delivery modes will accelerate basic research into human disease and open up new therapeutic possibilities.