Prof Chase Beisel
RNA Synthetic Biology
The lab of Chase Beisel investigates and harnesses the functional diversity of CRISPR-Cas immune systems for the development of new foundational technologies. They aim to develop a new generation of CRISPR technologies that can be employed to better understand, diagnose, and combat human infections.
Our research and approach
RNA is a ubiquitous molecule of life that plays intimate roles in how cells function and make decisions. These same properties can be harnessed to create a new generation of engineering tools to further interrogate the properties of biology and control how cells behave. The RNA synthetic biology group aims to better understand the roles RNA plays in biology and to exploit these roles to improve how we study, diagnose, and treat infectious diseases in humans.
Team members
Prof Chase Beisel
Group Leader
Dr Chunyu Liao
Postdoc
Dr Oleg Dmytrenko
Postdoc
Chunlei Jiao
PhD Student
Daphne Collias
PhD Student
Elena Vialetto
PhD Student
Franziska Wimmer
PhD Student
Katharina Wandera
PhD Student
Sandra Gawlitt
PhD Student
Jiaqi Yu
Technical Assistant
Tatjana Achmedov
Technical Assistant
Publications
2020
Methods for characterizing, applying, and teaching CRISPR-Cas systems
Beisel C (2020)
Methods (San Diego, Calif.)DOI: 10.1016/j.ymeth.2020.01.004
CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
Wimmer F, Beisel C (2020)
Front. Microbiol., 10: 1365DOI: 10.3389/fmicb.2019.03078
2019
Barriers to genome editing with CRISPR in bacteria
Vento J, Crook N, Beisel C (2019)
J Ind Microbiol Biotechnol, 46 (9-10): 1327-1341DOI: 10.1007/s10295-019-02195-1
Modular one-pot assembly of CRISPR arrays enables library generation and reveals factors influencing crRNA biogenesis
Liao C, Ttofali F, Slotkowski R, Denny S, Cecil T, Leenay R, Keung A, Beisel C (2019)
Nature Communications, 10 (1): 2948DOI: 10.1038/s41467-019-10747-3
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells
Pickar-Oliver A, Black J, Lewis M, Mutchnick K, Klann T, Gilcrest K, Sitton M, Nelson C, Barrera A, Bartelt L, …, Barrangou R, Gersbach C (2019)
Nat BiotechnolDOI: 10.1038/s41587-019-0235-7
Characterization of the all-E. coli transcription-translation system myTXTL by mass spectrometry
Garenne D, Beisel C, Noireaux V (2019)
Rapid Communications In Mass Spectrometry, 33 (11): 1036-1048DOI: 10.1002/rcm.8438
Distinct timescales of RNA regulators enable the construction of a genetic pulse generator
Westbrook A, Tang X, Marshall R, Maxwell C, Chappell J, Agrawal D, Dunlop M, Noireaux V, Beisel C, Lucks J, Franco E (2019)
Biotechnol Bioeng, 116 (5): 1139-1151DOI: 10.1002/bit.26918
An enhanced assay to characterize anti-CRISPR proteins using a cell-free transcription-translation system
Wandera K, Collins S, Wimmer F, Marshall R, Noireaux V, Beisel C (2019)
Methods (San Diego, Calif.) (19): 1046-2023DOI: 10.1016/j.ymeth.2019.05.014
CRATES: A one-step assembly method for Class 2 CRISPR arrays
Liao C, Slotkowski R, Beisel C (2019)
Methods Enzymol, 629: 493-511DOI: 10.1016/bs.mie.2019.04.011
The Acidaminococcus sp. Cas12a nuclease recognizes GTTV and GCTV as non-canonical PAMs
Jacobsen T, Liao C, Beisel C (2019)
FEMS microbiology letters, 366 (8): 085DOI: 10.1093/femsle/fnz085
2018
Mathematical Modeling of RNA-Based Architectures for Closed Loop Control of Gene Expression
Agrawal D, Tang X, Westbrook A, Marshall R, Maxwell C, Lucks J, Noireaux V, Beisel C, Dunlop M, Franco E (2018)
ACS Synth Biol, 7 (5): 1219-1228DOI: 10.1021/acssynbio.8b00040
CRISPR RNA-Dependent Binding and Cleavage of Endogenous RNAs by the Campylobacter jejuni Cas9
Dugar G, Leenay R, Eisenbart S, Bischler T, Aul B, Beisel C, Sharma C (2018)
Mol Cell, 69 (5): 893-905DOI: 10.1016/j.molcel.2018.01.032
Advances in CRISPR Technologies for Microbial Strain Engineering
Alper H, Beisel C (2018)
Biotechnol J, 13 (9): 18004DOI: 10.1002/biot.201800460
Bacterial Adaptation to the Host's Diet Is a Key Evolutionary Force Shaping Drosophila-Lactobacillus Symbiosis
Martino M, Joncour P, Leenay R, Gervais H, Shah M, Hughes S, Gillet B, Beisel C, Leulier F (2018)
Cell Host Microbe, 24 (1): 109-119DOI: 10.1016/j.chom.2018.06.001
The Francisella novicida Cas12a is sensitive to the structure downstream of the terminal repeat in CRISPR arrays
Liao C, Slotkowski R, Achmedov T, Beisel C (2018)
RNA biology, 16 (4): 404-412DOI: 10.1080/15476286.2018.1526537
A detailed cell-free transcription-translation-based assay to decipher CRISPR protospacer-adjacent motifs
Maxwell C, Jacobsen T, Marshall R, Noireaux V, Beisel C (2018)
Methods (San Diego, Calif.), 143: 48-57DOI: 10.1016/j.ymeth.2018.02.016
CRISPR tool puts RNA on the record
Beisel C (2018)
Nature, 562 (7727): 347-349DOI: 10.1038/d41586-018-06869-1
Genome Editing with CRISPR-Cas9 in Lactobacillus plantarum Revealed That Editing Outcomes Can Vary Across Strains and Between Methods
Leenay R, Vento J, Shah M, Martino M, Leulier F, Beisel C (2018)
Biotechnol J, 14 (3): 17005DOI: 10.1002/biot.201700583
Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications
Bober J, Beisel C, Nair N (2018)
Annu Rev Biomed Eng, 20: 277-300DOI: 10.1146/annurev-bioeng-062117-121019
Rapid and Scalable Characterization of CRISPR Technologies Using an E. coli Cell-Free Transcription-Translation System
Marshall R, Maxwell C, Collins S, Jacobsen T, Luo M, Begemann M, Gray B, January E, Singer A, He Y, Beisel C, Noireaux V (2018)
Mol Cell, 69 (1): 146-157DOI: 10.1016/j.molcel.2017.12.007
2017
Deciphering, Communicating, and Engineering the CRISPR PAM
Leenay R, Beisel C (2017)
J Mol Biol, 429 (2): 177-191DOI: 10.1016/j.jmb.2016.11.024
Short DNA containing χ sites enhances DNA stability and gene expression in E. coli cell-free transcription-translation systems
Marshall R, Maxwell C, Collins S, Beisel C, Noireaux V (2017)
Biotechnol Bioeng, 114 (9): 2137-41DOI: 10.1002/bit.26333
Toward a genetic tool development pipeline for host-associated bacteria
Waller M, Bober J, Nair N, Beisel C (2017)
Curr Opin Microbiol, 38: 156-164DOI: 10.1016/j.mib.2017.05.006
What Is the Role of Circuit Design in the Advancement of Synthetic Biology? Part 1
Beisel C (2017)
Cell Syst, 4 (4): 370-372DOI: 10.1016/j.cels.2017.04.003
Advancing the design and delivery of CRISPR antimicrobials
Fagen J, Collias D, Singh A, Beisel C (2017)
Curr Opin Biomed Eng, 4: 57-64DOI: 10.1016/j.cobme.2017.10.001
2016
Current and future prospects for CRISPR-based tools in bacteria
Luo M, Leenay R, Beisel C (2016)
Biotechnol Bioeng, 113 (5): 930-43DOI: 10.1002/bit.25851
Rethinking the Hierarchy of Sugar Utilization in Bacteria
Beisel C, Afroz T (2016)
J Bacteriol, 198 (3): 374-376DOI: 10.1128/JB.00890-15
The CRISPR RNA-guided surveillance complex in Escherichia coli accommodates extended RNA spacers
Luo M, Jackson R, Denny S, Tokmina-Lukaszewska M, Maksimchuk K, Lin W, Bothner B, Wiedenheft B, Beisel C (2016)
Nucleic Acids Res, 44 (15): 7385-94DOI: 10.1093/nar/gkw421
Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems
Leenay R, Maksimchuk K, Slotkowski R, Agrawal R, Gomaa A, Briner A, Barrangou R, Beisel C (2016)
Mol Cell, 62 (1): 137-47DOI: 10.1016/j.molcel.2016.02.031
2015
Repurposing endogenous type I CRISPR-Cas systems for programmable gene repression
Luo M, Mullis A, Leenay R, Beisel C (2015)
Nucleic Acids Res, 43 (1): 674-81DOI: 10.1093/nar/gku971
Efficient Delivery of CRISPR-Cas9 for Genome Editing via Self-Assembled DNA Nanoclews**
Sun W, Ji W, Hall J, Hu Q, Wang C, Beisel C, Gu Z (2015)
Angew Chem Int Ed Engl, 54 (41): 12029-33DOI: 10.1002/anie.201506030
Impact of Residual Inducer on Titratable Expression Systems
Afroz T, Luo M, Beisel C (2015)
Plos One, 10 (9): 01374DOI: 10.1371/journal.pone.0137421
Trade-offs in engineering sugar utilization pathways for titratable control
Afroz T, Biliouris K, Boykin K, Kaznessis Y, Beisel C (2015)
ACS Synth Biol, 4 (2): 141-9DOI: 10.1021/sb400162z
2014
Construction of ligand-responsive microRNAs that operate through inhibition of Drosha processing
Beisel C, Bloom R, Smolke C (2014)
In: Artificial Riboswitches (ed Ogawa A), Methods Mol Biol, 1111: 259-67DOI: 10.1007/978-1-62703-755-6_19
Guide RNA functional modules direct Cas9 activity and orthogonality
Briner A, Donohoue P, Gomaa A, Selle K, Slorach E, Nye C, Haurwitz R, Beisel C, May A, Barrangou R (2014)
Mol Cell, 56 (2): 333-339DOI: 10.1016/j.molcel.2014.09.019
Bacterial sugar utilization gives rise to distinct single-cell behaviours
Afroz T, Biliouris K, Kaznessis Y, Beisel C (2014)
Mol Microbiol, 93 (6): 1093-1103DOI: 10.1111/mmi.12695
Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems
Gomaa A, Klumpe H, Luo M, Selle K, Barrangou R, Beisel C (2014)
MBio, 5 (1): 00928-13DOI: 10.1128/mBio.00928-13
A CRISPR design for next-generation antimicrobials
Beisel C, Gomaa A, Barrangou R (2014)
Genome Biol, 15 (11): 516DOI: 10.1186/s13059-014-0516-x
2013
Understanding and exploiting feedback in synthetic biology
Afroz T, Beisel C (2013)
Chem Eng Sci, 103: 79-90DOI: 10.1016/j.ces.2013.02.017
2012
Multiple factors dictate target selection by Hfq-binding small RNAs
Beisel C, Updegrove T, Janson B, Storz G (2012)
EMBO J, 31 (8): 1961-74DOI: 10.1038/emboj.2012.52
2011
Discriminating tastes: physiological contributions of the Hfq-binding small RNA Spot 42 to catabolite repression
Beisel C, Storz G (2011)
RNA biology, 8 (5): 766-70DOI: 10.4161/rna.8.5.16024
Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing
Beisel C, Chen Y, Culler S, Hoff K, Smolke C (2011)
Nucleic Acids Res, 39 (7): 2981-94DOI: 10.1093/nar/gkq954
The base pairing RNA Spot 42 participates in a multi-output feedforward loop to help enact catabolite repression in Escherichia coli
Beisel C, Storz G (2011)
Mol Cell, 41 (3): 286-97DOI: 10.1016/j.molcel.2010.12.027
2010
Base pairing small RNAs and their roles in global regulatory networks
Beisel C, Storz G (2010)
FEMS Microbiol Rev, 34 (5): 866-82DOI: 10.1111/j.1574-6976.2010.00241.x
2009
Synthetic control of a fitness tradeoff in yeast nitrogen metabolism
Bayer T, Hoff K, Beisel C, Lee J, Smolke C (2009)
J Biol Eng, 3: 1DOI: 10.1186/1754-1611-3-1
Design Principles for Riboswitch Function
Beisel C, Smolke C (2009)
PLos Comput Biol, 5 (4): 10003DOI: 10.1371/journal.pcbi.1000363
2008
Model-guided design of ligand-regulated RNAi for programmable control of gene expression
Beisel C, Bayer T, Hoff K, Smolke C (2008)
Mol Syst Biol, 4: 224DOI: 10.1038/msb.2008.62
2005
Conformational analysis of gossypol and its derivatives by molecular mechanics
Beisel C, Dowd M, Reilly P (2005)
J Mol Struc-Theochem, 730 (1-3): 51-58DOI: 10.1016/j.theochem.2005.05.010
2002
Cochlear whole mount in situ hybridization: identification of longitudinal and radial gradients
Judice T, Nelson N, Beisel C, Delimont D, Fritzsch B, Beisel K (2002)
Brain Res Protoc, 9 (1): 65-76DOI: 10.1016/S1385-299X(01)00138-6
Research projects
RNA traditionally is viewed as a passive information carrier that connect our genomic blueprints to the sets of proteins that determine how each cell behaves. However, the past decade has revealed a myriad of other functions that continues to reshape our understanding of this versatile biomolecule. These insights range from how RNA directs tissue development to aiding how bacteria sense and respond to their environment. From an engineering perspective, each discovery creates the opportunity to develop new technologies to improve how we gauge our health and treat diseases that afflict us.
One of the greatest examples was the discovery of RNAs involved in adaptive immune systems in bacteria and archaea called CRISPR-Cas systems. These systems use RNA to recognize matching genetic material from selfish genetic elements bent on infecting these microbes. However, this property was quickly co-opted to form powerful tools that easily and selectively cut matching DNA sequences, which is revolutionizing our ability to edit DNA sequences at will —whether in industrial bacteria to overproduce therapeutic compounds or in humans to cure otherwise untreatable genetic diseases. These same CRISPR technologies are also being applied to rapidly and cheaply diagnose viral infections and to serve as tailored-spectrum antimicrobials that can selectively eradicate pathogens while sparing our commensal microbiota.
CRISPR technologies hold incredible potential, yet they are derived from immune systems that we are still trying to understand. We are exploring the full diversity of these immune systems in nature and how their functions have evolved to protect microbes against foreign invaders. We are also using these insights to advance how we study infectious disease and how we combat multidrug-resistant infections.