Uncovering the principles of molecular design for biology, medicine and biotechnology
Our research
We are a group of energetic scientists driven to understand and improve our relationship with the natural world. Our molecule of interest, RNA, is similar to DNA, but is more versatile within the cell. We study how the structure of RNA plays a role in its cellular jobs, how cells use molecules like RNA to monitor and respond to their changing environments, and how we can use these molecules in cell-free systems to monitor our own environments for health and sustainability.
News
Northwestern University scientists sprint to develop new kind of rapid coronavirus test, Chicago Tribune
Simple test could prevent fluoride-related disease, Science Daily
Recent Publications
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Improving fold activation of small transcription activating RNAs (STARs) with rational RNA engineering strategies
S. Meyer, J. Chappell, S. Sankar, R. Chew, J. B. Lucks. Biotechnology and Bioengineering. (2015). doi: 10.1002/bit.25693
Links: Journal, PDF, bioRxiv (Open Access), Blog Post: Sarai’s paper featured in B&B spotlight! and Improving STARs with rational RNA engineering strategies.About
Here, we demonstrate varies strategies for improving upon the capacity of everyone’s favorite RNA regulators, small transcription activating RNAs (STARs). We showcase general rules for enhancing STARs’ fold activity through the combination of expression level tuning and RNA engineering design. These enhanced antisense regulators continue to demonstrate their tremendous orthogonality against both each other and panels of antisense RNA repressors. This work serves to augment the utility of the STARs toolkit providing researchers with a means for precision control over transcription-level gene expression.
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A renaissance in RNA synthetic biology: new mechanisms, applications and tools for the future
J. Chappell, K. E. Watters, M. K. Takahashi, J. B. Lucks. Current Opinion in Chemical Biology. (2015). doi: 10.1016/j.cbpa.2015.05.018
Links: Journal, PDF, Blog PostAbout
Advances in RNA mechanism design tools have expanded the dynamic range and orthogonality of RNA-based synthetic mechanisms. This paper explains how these improvements can expand RNA genetic circuit applications, including those in metabolic engineering and diagnostics. It then describes how experimental and computational RNA structural tools can further improve our understanding of these mechanisms.
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Generating effective models and parameters for RNA genetic circuits
C. Y. Hu, J. D. Varner, J. B. Lucks. ACS Synthetic Biology. (2015). doi: 10.1021/acssynbio.5b00077
Links: Journal, PDF, BioRxiv (Open Access), Code: GitHub, Blog PostAbout
This paper seeks to understand how to parameterize models of RNA regulation using E. coli cell-free extracts by outlining a defined set of simple experiments that can rapidly and quantitatively inform new designs. These models can effectively predict the performance of a transcriptional genetic cascade, when provided the network topology and the concentration of each component.
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Creating Small Transcription Activating RNAs
J. Chappell, M. K. Takahashi, J. B. Lucks. Nature Chemical Biology. (2015). doi: 10.1038/NCHEMBIO.1737
Links: Journal, PDF, Supplemental InfoAbout
This is the first work to create and characterize small transcription activating RNAs, known as STARS. STARS are antisense RNAs that activate transcription of their target by disrupting a terminator in the sense RNA. This work demonstrates the versatility of STARs in cells and in vitro, as well as on both natural and synthetic target RNAs.
Blog Posts
- STARs are born in Nature Chemical Biology!
- STARs are on the front page of the Nature Chemical Biology Website!
- STARs Paper Among Most Read on Nature Chemical Biology Site!
Commentary: N. Rusk. “Synthetic biology: RNA that activates transcription.”, Nature Methods, 2015, 12, 290.
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SHAPE-Seq 2.0: Systematic optimization and extension of high-throughput chemical probing of RNA secondary structure with next-generation sequencing
D. Loughrey#, K. E. Watters#, A. Settle, J. B. Lucks. Nucleic Acids Research. (2014). (* Co-first author) doi: 10.1093/nar/gku909 # = Equal contribution
Links: Journal, PDF, SHAPE-Seq DataSets: RMDB Entries.About
In this paper, we analyze and optimize SHAPE-seq, a technique for probing RNA structures. The results present an updated SHAPE-Seq protocol, v2.0, which can obtain reactivity information for every nucleotide of an RNA without requiring an internal RT priming site.