UNDERSTANDING AND ENGINEERING LIFE THROUGH RNA
The goal of the Chappell lab is to forward our ability to understand and engineer the bacteria domain of life. Central to this is our ability to control how cells express their genetic information. Our lab focuses on understanding how the biomolecule RNA can be designed to create synthetic regulators of gene expression—allowing for the manipulation of natural cellular processes to elicit deeper biological understanding and for the engineering of new synthetic cellular functions. As such our lab focuses both on the creation of new gene regulatory tools and their application.
RNA-based tools to reprogram endogenous gene expression.
Gene expression is at the heart of how cells control functions, phenotypes, and differentiation. 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. Our goals are to (i) create new tools for reprogramming bacterial gene expression, for example CRISPR-Cas based activators (CRISPRa), and (ii) apply these tools in bacterial species important to biotechnology and biomedicine, currently focused on Streptomyces species. Our interest in Streptomyces is due to their robust secondary metabolism and abundance of natural products with useful bioactive properties, such as antibiotics.
Plug-and-play RNA sensing systems.
Our laboratory is interested in creating novel RNA sense and response devices able to detect (i) RNA signatures and (ii) small molecules. Our goal is to use these genetically-encoded sensors to reprogram cells for therapeutic and diagnostic purposes. This work is currently focused on creating sensors from catalytic RNAs (ribozymes) using novel biomolecular engineering approaches.
RNA-based synthetic gene circuits.
At the heart of bacteria’s ability to make decisions are regulatory networks that allow cells to convert cellular and environmental information into changes of gene expression. Our goal has been to advance the use of synthetic RNA regulators to create regulatory gene networks that operate through RNA signals. We are currently interested in (i) creating RNA networks that function in diverse bacterial hosts and (ii) creating RNA-only dynamic circuits.