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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Zur and Zinc Increase Expression of E. coli Ribosomal Protein L31 Through RNA-Mediated Repression of the Repressor L31p
R. A. Rasmussen, S. Wang, J. M. Camarillo, V. Sosnowski, B-K. Cho, Y. A. Goo, J. B. Lucks, T. V. O’Halloran. Nucleic Acids Research (2022). doi: 10.1101/2022.05.27.493739
Links: Journal, PDFAbout
We elucidate a new mechanism in this work that explains how E. coli switch one of their ribosomal proteins to adapt to the environmental stress zinc depletion. We find that one form of this ribosomal protein, which is regulated by a zinc-sensing transcription factor, represses production of the other protein by binding to its mRNA in a structure-dependent manner.
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Cotranscriptional RNA strand exchange underlies the gene regulation mechanism in a purine-sensing transcriptional riboswitch
L. Cheng, E. N. White, N. L. Brandt, A. M. Yu, A. A. Chen, J. B. Lucks. Nucleic Acids Research (2022). doi: 10.1101/2021.10.25.465737
Links: Journal, PDF, BioRxivAbout
Our work in this paper studies how RNA cotranscriptional folding is involved in the mechanism of a transcriptional purine-sensing riboswitch. We used a combination of SHAPE-Seq structural probing, cellular fluorescence assays, and all-atom molecular dynamics simulations that suggested an intermediate structure undergoes strand exchange to mediate between the anti-terminated and terminated states of the riboswitch.
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How does RNA fold dynamically?
Bushhouse, D.Z., Choi, E.K., Hertz, L.M. and Lucks, J.B.*, Journal of Molecular Biology (2022) doi:10.1016/j.jmb.2022.167665
Links: Journal, PDFAbout
In this perspective, we engage three questions regarding RNA cotranscriptional folding:
1) What is the Appropriate Biophysical Framework to Describe Non- equilibrium Conformational Switching?
2) How Widespread is Strand Displacement as a General Feature of RNA Conformational Switching?
3) How do Proteins Mediate Cotranscriptional RNA Conformational Switching? -
Engineering a Synthetic Dopamine-Responsive Riboswitch for In Vitro Biosensing
Harbaugh S. V., Silverman A. D., Chushak Y. G., Zimlich K., Wolfe M., Thavarajah W., Jewett M. C., Lucks J. B., Chávez J. L. ACS Synthetic Biology (2022). doi:10.1021/acssynbio.1c00560
Links: Journal, PDFAbout
This paper uses RNA engineering to create a synthetic RNA riboswitch to detect dopamine in cell-free diagnostic systems. Use of control reactions allows an assay format to control for matrix inhibition when testing human samples.
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Programming cell-free biosensors with DNA strand displacement circuits
K. J. Jung#, K. K. Alam#, C. M. Archuleta, J. B. Lucks*. (2022). Nature Chemical Biology (2022). doi:10.1038/s41589-021-00962-9.
Link: Journal, PDFAbout
Here we extend the ROSALIND cell-free biosensor platform with toe-hold mediated DNA strand displacement (TMSD) circuits. TMSD produces rapid signal generation, and provides a powerful approach to creating information processing circuits that improve and enhance biosensor function. We use TMSD to build 12 different logic gates that implement a range of functions (NOT, OR, AND, IMPLY, NOR, NIMPLY, NAND), as well as an analog-to-digital conversion circuit that gives semi-quantitative read outs.
News and Views: “Logic invades cell-free biosensing.” E. Amalfatino and K. Pardee, Nature Chemical Biology, doi:10.1038/s41589-021-00963-8.