About
James Chappell is an Assistant Professor in the Biosciences department at Rice University. He received his PhD from Imperial College London and performed post-doctoral research at Cornell and Northwestern University. His research focuses on developing synthetic and systems biology approaches to understand and engineer microbial communities, with particular interest in microbial signaling, gene regulation, and microbiome homeostasis. His work involves creating programmable RNA-based therapeutics and biosensors, as well as enhancing the target specificity of ribozymes and other RNA tools for environmental and health applications. Dr. Chappell's contributions aim to address global health challenges and advance our understanding of microbial interactions and gene regulation.
Research topics
- Computer Science
- Genetics
- Biology
- Computational biology
- Cell biology
- World Wide Web
- Operating system
- Biochemistry
Selected publications
A split ribozyme that links detection of a native RNA to orthogonal protein outputs
Nature Communications · 2023 · 38 citations
Senior authorCorresponding- Computational biology
- Biology
- Cell biology
Individual RNA remains a challenging signal to synthetically transduce into different types of cellular information. Here, we describe Ribozyme-ENabled Detection of RNA (RENDR), a plug-and-play strategy that uses cellular transcripts to template the assembly of split ribozymes, triggering splicing reactions that generate orthogonal protein outputs. To identify split ribozymes that require templating for splicing, we use laboratory evolution to evaluate the activities of different split variants of the Tetrahymena thermophila ribozyme. The best design delivers a 93-fold dynamic range of splicing with RENDR controlling fluorescent protein production in response to an RNA input. We further resolve a thermodynamic model to guide RENDR design, show how input signals can be transduced into diverse outputs, demonstrate portability across different bacteria, and use RENDR to detect antibiotic-resistant bacteria. This work shows how transcriptional signals can be monitored in situ and converted into different types of biochemical information using RNA synthetic biology.
Nucleic Acids Research · 2022 · 67 citations
Senior authorCorresponding- Computer Science
- Biology
- Genetics
The rise of antibiotic-resistant bacteria represents a major threat to global health, creating an urgent need to discover new antibiotics. Natural products derived from the genus Streptomyces represent a rich and diverse repertoire of chemical molecules from which new antibiotics are likely to be found. However, a major challenge is that the biosynthetic gene clusters (BGCs) responsible for natural product synthesis are often poorly expressed under laboratory culturing conditions, thus preventing the isolation and screening of novel chemicals. To address this, we describe a novel approach to activate silent BGCs through rewiring endogenous regulation using synthetic gene regulators based upon CRISPR-Cas. First, we refine CRISPR interference (CRISPRi) and create CRISPR activation (CRISPRa) systems that allow for highly programmable and effective gene repression and activation in Streptomyces. We then harness these tools to activate a silent BGC by perturbing its endogenous regulatory network. Together, this work advances the synthetic regulatory toolbox for Streptomyces and facilitates the programmable activation of silent BGCs for novel chemical discovery.
Nucleic Acids Research · 2021 · 42 citations
Senior authorCorresponding- Computer Science
- Biology
- Computational biology
CRISPR-Cas activator (CRISPRa) systems that selectively turn on transcription of a target gene are a potentially transformative technology for programming cellular function. While in eukaryotes versatile CRISPRa systems exist, in bacteria these systems suffer from a limited ability to activate different genes due to strict distance-dependent requirements of functional target binding sites, and require greater customization to optimize performance in different genetic and cellular contexts. To address this, we apply a rational protein engineering approach to create a new CRISPRa platform that is highly modular to allow for easy customization and has increased targeting flexibility through harnessing engineered Cas proteins. We first demonstrate that transcription activation domains can be recruited by CRISPR-Cas through noncovalent protein-protein interactions, which allows each component to be encoded on separate and easily interchangeable plasmid elements. We then exploit this modularity to rapidly screen a library of different activation domains, creating new systems with distinct regulatory properties. Furthermore, we demonstrate that by harnessing a library of circularly permuted Cas proteins, we can create CRISPRa systems that have different target binding site requirements, which together, allow for expanded target range.
Recent grants
Frequent coauthors
- 22 shared
Julius B. Lucks
Northwestern University
- 14 shared
Chase L. Beisel
Helmholtz Institute for RNA-based Infection Research
- 13 shared
Boris Draznin
- 12 shared
J. Wayne Leitner
- 11 shared
Vincent Noireaux
University of Minnesota
- 11 shared
Elisa Franco
University of California, Los Angeles
- 9 shared
Melanie S. Reece
University of Colorado Denver
- 9 shared
Richard O. Jones
Johns Hopkins University
Labs
Education
- 2013
PhD, Molecular Biosciences
Imperial College London
- 2008
Bsc, Biochemistry
Imperial College London
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