Engineering microbes and microbiomes using RNA
The goal of the Chappell lab is to forward our ability to study and engineer microbiomes and non-model microbes using RNA-based technologies. We are interested in engineering RNA to create synthetic regulators, memory devices, sensors, and gene circuits. We then apply these technologies for basic science investigations and applications in health and the environment.
1. Synthetic gene regulators for programming genomes
Gene expression is at the heart of how cells control functions and phenotypes. As such, the ability to reprogram how a cell expresses its genome is a potentially transformative capability to uncover gene function or induce valuable phenotypes. We have been creating new tools for reprogramming bacterial gene expression, for example, CRISPR-Cas based activators (CRISPRa) that turn on transcription of a target gene. Applications of these technologies include turning on the expression of silent biosynthetic gene clusters (BGCs) in Streptomyces for antibiotic discovery applications.
2. Plug-and-play RNA sensing and memory systems
Our laboratory is interested in creating novel RNA sense and response devices able to detect RNA signatures. We are using these technologies to control genetic programs in response to host RNAs for biomedical applications. Additionally, we are creating novel RNA-based memory systems that can be used to convert cellular events (e.g., gene transfer, sensing small molecules) into genetic memories that can be later read out by sequencing. We are using these technologies for microbiome engineering applications of relevance to the environmental and health.
3. Synthetic Gene nETWORKS AND SYNTHETIC CELLS
At the heart of how cells make decisions are regulatory networks that allow cells to convert cellular and environmental information into changes of gene expression. Our lab has a long-standing interest in creating and applying synthetic RNA regulators to make synthetic regulatory gene networks, towards creating synthetic cells.