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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ROSALIND: Rapid Detection of Chemical Contaminants with In Vitro Transcription Factor-Based Biosensors
J. K. Jung, K. K. Alam, J.B. Lucks*. Cell-Free Gene Expression, pp. 325-342 (2022).
Links: BookAbout
This paper outlines detailed protocols for assembling ROSALIND cell-free biosensing reactions. Includes protocols for making reagents (DNA templates, purified transcription factors) as well.
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RNA Engineering for Public Health: Innovations in RNA-Based Diagnostics and Therapeutics
W. Thavarajah#, L. M. Hertz#, D. Z. Bushhouse, C. M. Archuleta, and J.B. Lucks*. Annual Reviews (2021). doi: 10.1146/annurev-chembioeng-101420-014055, # = Equal contribution
Links: Journal, PDFAbout
This review describes recent applications in RNA engineering to develop the next generation of diagnostics and therapeutics. It covers sensors for both chemicals and pathogens, CRISPR technologies, mRNA vaccines, and the future of personalized medicine with RNA-targeting drugs. We wrap up with a perspective on the future of the field with its coming challenges and opportunities.
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Dynamic control of gene expression with riboregulated switchable feedback promoters
C.J. Glasscock, J.T. Lazar, B.W. Biggs, J.H. Arnold, M-K Kang, D. Tullman-Ercek, K.E.J. Tyo, J.B. Lucks*. ACS Synthetic Biology (2021). doi: 10.1021/acssynbio.1c00015
Links: Journal, PDF, BioRxivAbout
This paper presents a new mechanism for controlling cellular stress response networks with RNA regulators. The insertion of a small transcription activating RNA switch behind stress response promoters allows optimization of metabolic pathway production via induction timing, magnitude and even autonomous quorum sensing-mediated activation.
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RNA sequence and structure determinants of Pol III transcriptional termination in human cells
Matthew S. Verosloff, William K. Corcoran, Taylor B. Dolberg, Joshua N. Leonard*, J.B. Lucks*. Journal of Molecular Biology (2021). doi: 10.1016/j.jmb.2021.166978
Links: Journal, PDF, BioRxivAbout
Here, we present work aimed at furthering our understanding of human RNA Polymerase III termination. To accomplish this, we developed a novel in celluo assay that allows for quantification of termination events. We demonstrated that in our system termination only occurs when poly-U tracts are longer than the average lengths found within the human genome. We found that placing secondary structure, immediately upstream of these tracts, within the nascent RNA enabled efficient termination at shorter but representative poly-U tract lengths. This impact decreases as we moved the structural motif further upstream from the poly-U tract.
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Computationally reconstructing cotranscriptional folding pathways from experimental data reveals rearrangement of non-native folding intermediates
A. M. Yu, P. M. Gasper, L. Cheng, L. B. Lai#, S. Kaur#, V. Gopalan, A. A. Chen, J. B. Lucks*. Molecular Cell (2021) doi: 10.1016/j.molcel.2020.12.017 # = Equal contribution
Links: Journal, PDF, BioRxivAbout
This paper presents a new method – reconstructing RNA dynamics from data (R2D2) – that combines high throughput chemical probing of RNA structure with computational structure prediction, to reconstruct cotranscriptional folding pathways from RNAs. Integration with all-atom 3D simulations allows mechanistic investigation into cotranscriptional RNA structure rearrangements. Application to the bacterial signal recognition particle (SRP) RNA strongly suggests a role for toehold mediated strand displacement in resolving kinetic traps in cotranscriptional folding pathways.