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 Ioannis Mougiakos
Postdoc

Dr Oleg Dmytrenko
Postdoc

Dr Srinivas Manchalu
Postdoc

Chunlei Jiao
PhD Student

Daphne Collias
PhD Student

Elena Vialetto
PhD Student

Frank Englert
PhD Student

Franziska Wimmer
PhD Student

Katharina Wandera
PhD Student

Sandra Gawlitt
PhD Student

Dr Anzhela Migur
Technical Assistant

Jiaqi Yu
Technical Assistant

Tatjana Achmedov
Technical Assistant
Natalia Luise Peeck
Master Student
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.
Publications
2020
A positive, growth-based PAM screen identifies noncanonical motifs recognized by the S. pyogenes Cas9
Collias D, Leenay RT, Slotkowski RA, Zuo Z, Collins SP, McGirr BA, Liu J, Beisel CL (2020)
Science Advances, 6 (29): 4054
Your Base Editor Might Be Flirting with Single (Stranded) DNA: Faithful On-Target CRISPR Base Editing without Promiscuous Deamination
Collins SP, Beisel CL (2020)
Molecular Cell, 79 (5): 703-704
Characterization of Cas12a nucleases reveals diverse PAM profiles between closely-related orthologs
Jacobsen T, Ttofali F, Liao C, Manchalu S, Gray BN, Beisel CL (2020)
Nucleic Acids Research, 48 (10): 5624-5638
Rapid Testing of CRISPR Nucleases and Guide RNAs in an E. coli Cell-Free Transcription-Translation System
Marshall R, Beisel CL, Noireaux V (2020)
STAR Protocols, 1 (1): 10000
Tunable self-cleaving ribozymes for modulating gene expression in eukaryotic systems
Jacobsen T, Yi G, Al Asafen H, Jermusyk AA, Beisel CL, Reeves GT (2020)
PLOS One, 15 (4): 02320
Competitive exclusion is a major bioprotective mechanism of lactobacilli against fungal spoilage in fermented milk products
Siedler S, Rau MH, Bidstrup S, Vento JM, Aunsbjerg SD, Bosma EF, McNair LM, Beisel CL, Neves AR (2020)
Applied and Environmental Microbiology, 86 (7): 02312-19
Methods for characterizing, applying, and teaching CRISPR-Cas systems
Beisel CL (2020)
Methods, 172: 1-2
CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
Wimmer F, Beisel CL (2020)
Frontiers in Microbiology, 10: 3078
2019
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells
Pickar-Oliver A, Black JB, Lewis MM, Mutchnick KJ, Klann TS, Gilcrest KA, Sitton MJ, Nelson CE, Barrera A, Bartelt LC, …, Barrangou R, Gersbach CA (2019)
Nature Biotechnology, 37 (12): 1493-1501
Modular one-pot assembly of CRISPR arrays enables library generation and reveals factors influencing crRNA biogenesis
Liao C, Ttofali F, Slotkowski RA, Denny SR, Cecil TD, Leenay RT, Keung AJ, Beisel CL (2019)
Nature Communications, 10: 2948
An educational module to explore CRISPR technologies with a cell-free transcription-translation system
Collias D, Marshall R, Collins SP, Beisel CL, Noireaux V (2019)
Synthetic Biology, 4 (1): 156
CRATES: A one-step assembly method for Class 2 CRISPR arrays
Liao C, Slotkowski RA, Beisel CL (2019)
Methods In Enzymology, 629: 493-511
Barriers to genome editing with CRISPR in bacteria
Vento JM, Crook N, Beisel CL (2019)
Journal of Industrial Microbiology & Biotechnology, 46 (9-10): 1327-1341
Characterization of the all-E. coli transcription-translation system myTXTL by mass spectrometry
Garenne D, Beisel CL, Noireaux V (2019)
Rapid Communications In Mass Spectrometry, 33 (11): 1036-1048
Distinct timescales of RNA regulators enable the construction of a genetic pulse generator
Westbrook A, Tang X, Marshall R, Maxwell CS, Chappell J, Agrawal DK, Dunlop MJ, Noireaux V, Beisel CL, Lucks J, Franco E (2019)
Biotechnology and Bioengineering, 116 (5): 1139-1151
An enhanced assay to characterize anti-CRISPR proteins using a cell-free transcription-translation system
Wandera KG, Collins SP, Wimmer F, Marshall R, Noireaux V, Beisel CL (2019)
Methods, 172: 42-50
The Acidaminococcus sp. Cas12a nuclease recognizes GTTV and GCTV as non-canonical PAMs
Jacobsen T, Liao C, Beisel CL (2019)
FEMS Microbiology Letters, 366 (8): 085
2018
Bacterial Adaptation to the Host's Diet Is a Key Evolutionary Force Shaping Drosophila-Lactobacillus Symbiosis
Martino ME, Joncour P, Leenay R, Gervais H, Shah M, Hughes S, Gillet B, Beisel CL, Leulier F (2018)
Cell Host & Microbe, 24 (1): 109-119
Rapid and Scalable Characterization of CRISPR Technologies Using an E. coli Cell-Free Transcription-Translation System
Marshall R, Maxwell CS, Collins SP, Jacobsen T, Luo ML, Begemann MB, Gray BN, January E, Singer A, He Y, Beisel CL, Noireaux V (2018)
Molecular Cell, 69 (1): 146-157
CRISPR RNA-Dependent Binding and Cleavage of Endogenous RNAs by the Campylobacter jejuni Cas9
Dugar G, Leenay RT, Eisenbart SK, Bischler T, Aul BU, Beisel CL, Sharma CM (2018)
Molecular Cell, 69 (5): 893-905
Advances in CRISPR Technologies for Microbial Strain Engineering
Alper HS, Beisel CL (2018)
Biotechnology Journal, 13 (9): 18004
Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications
Bober JR, Beisel CL, Nair NU (2018)
Annual Review of Biomedical Engineering, 20: 277-300
Mathematical Modeling of RNA-Based Architectures for Closed Loop Control of Gene Expression
Agrawal DK, Tang X, Westbrook A, Marshall R, Maxwell CS, Lucks J, Noireaux V, Beisel CL, Dunlop MJ, Franco E (2018)
ACS Synthetic Biology, 7 (5): 1219-1228
A detailed cell-free transcription-translation-based assay to decipher CRISPR protospacer-adjacent motifs
Maxwell CS, Jacobsen T, Marshall R, Noireaux V, Beisel CL (2018)
Methods, 143: 48-57
Genome Editing with CRISPR-Cas9 in Lactobacillus plantarum Revealed That Editing Outcomes Can Vary Across Strains and Between Methods
Leenay RT, Vento JM, Shah M, Martino ME, Leulier F, Beisel CL (2018)
Biotechnology Journal, 14 (3): 17005
The Francisella novicida Cas12a is sensitive to the structure downstream of the terminal repeat in CRISPR arrays
Liao C, Slotkowski RA, Achmedov T, Beisel CL (2018)
RNA Biology, 16 (4): 404-412
2017
What Is the Role of Circuit Design in the Advancement of Synthetic Biology? Part 1
Beisel CL (2017)
Cell Systems, 4 (4): 370-372
Deciphering, Communicating, and Engineering the CRISPR PAM
Leenay RT, Beisel CL (2017)
Journal of Molecular Biology, 429 (2): 177-191
Toward a genetic tool development pipeline for host-associated bacteria
Waller MC, Bober JR, Nair NU, Beisel CL (2017)
Current Opinion in Microbiology, 38: 156-164
Short DNA containing χ sites enhances DNA stability and gene expression in E. coli cell-free transcription-translation systems
Marshall R, Maxwell CS, Collins SP, Beisel CL, Noireaux V (2017)
Biotechnology and Bioengineering, 114 (9): 2137-41
Advancing the design and delivery of CRISPR antimicrobials
Fagen JR, Collias D, Singh AK, Beisel CL (2017)
Current Opinion in Biomedical Engineering, 4: 57-64
2016
The CRISPR RNA-guided surveillance complex in Escherichia coli accommodates extended RNA spacers
Luo ML, Jackson RN, Denny SR, Tokmina-Lukaszewska M, Maksimchuk KR, Lin W, Bothner B, Wiedenheft B, Beisel CL (2016)
Nucleic Acids Research, 44 (15): 7385-94
Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems
Leenay RT, Maksimchuk KR, Slotkowski RA, Agrawal RN, Gomaa AA, Briner AE, Barrangou R, Beisel CL (2016)
Molecular Cell, 62 (1): 137-47
Synthetic Biology - Engineering Genes with CRISPR-Cas9
Luo ML, Beisel CL (2016)
CEP Magazine, September
Rethinking the Hierarchy of Sugar Utilization in Bacteria
Beisel CL, Afroz T (2016)
Journal of Bacteriology, 198 (3): 374-376
Current and future prospects for CRISPR-based tools in bacteria
Luo ML, Leenay RT, Beisel CL (2016)
Biotechnology and Bioengineering, 113 (5): 930-43
2015
Efficient Delivery of CRISPR-Cas9 for Genome Editing via Self-Assembled DNA Nanoclews**
Sun W, Ji W, Hall JM, Hu Q, Wang C, Beisel CL, Gu Z (2015)
Angewandte Chemie International Edition, 54 (41): 12029-33
Trade-offs in engineering sugar utilization pathways for titratable control
Afroz T, Biliouris K, Boykin KE, Kaznessis Y, Beisel CL (2015)
ACS Synthetic Biology, 4 (2): 141-9
Impact of Residual Inducer on Titratable Expression Systems
Afroz T, Luo ML, Beisel CL (2015)
PLOS One, 10 (9): 01374
Repurposing endogenous type I CRISPR-Cas systems for programmable gene repression
Luo ML, Mullis AS, Leenay RT, Beisel CL (2015)
Nucleic Acids Research, 43 (1): 674-81
2014
A CRISPR design for next-generation antimicrobials
Beisel CL, Gomaa AA, Barrangou R (2014)
Genome Biology, 15 (11): 516
Guide RNA functional modules direct Cas9 activity and orthogonality
Briner AE, Donohoue PD, Gomaa AA, Selle K, Slorach EM, Nye CH, Haurwitz RE, Beisel CL, May AP, Barrangou R (2014)
Molecular Cell, 56 (2): 333-339
Construction of ligand-responsive microRNAs that operate through inhibition of Drosha processing
Beisel CL, Bloom RJ, Smolke CD (2014)
In: Artificial Riboswitches (ed Ogawa A), Methods Mol Biol, 1111: 259-67
Bacterial sugar utilization gives rise to distinct single-cell behaviours
Afroz T, Biliouris K, Kaznessis Y, Beisel CL (2014)
Molecular Microbiology, 93 (6): 1093-1103
Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems
Gomaa AA, Klumpe HE, Luo ML, Selle K, Barrangou R, Beisel CL (2014)
mBio, 5 (1): 00928-13
2013
Understanding and exploiting feedback in synthetic biology
Afroz T, Beisel CL (2013)
Chemical Engineering Science, 103: 79-90
2012
Multiple factors dictate target selection by Hfq-binding small RNAs
Beisel CL, Updegrove TB, Janson BJ, Storz G (2012)
The EMBO Journal, 31 (8): 1961-74
2011
The base pairing RNA Spot 42 participates in a multi-output feedforward loop to help enact catabolite repression in Escherichia coli
Beisel CL, Storz G (2011)
Molecular Cell, 41 (3): 286-97
Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing
Beisel CL, Chen YY, Culler SJ, Hoff KG, Smolke CD (2011)
Nucleic Acids Research, 39 (7): 2981-94
Discriminating tastes: physiological contributions of the Hfq-binding small RNA Spot 42 to catabolite repression
Beisel CL, Storz G (2011)
RNA Biology, 8 (5): 766-70
2010
Base pairing small RNAs and their roles in global regulatory networks
Beisel CL, Storz G (2010)
FEMS Microbiology Reviews, 34 (5): 866-82
2009
Synthetic control of a fitness tradeoff in yeast nitrogen metabolism
Bayer TS, Hoff KG, Beisel CL, Lee JJ, Smolke CD (2009)
Journal of Biological Engineering, 3: 1
Design Principles for Riboswitch Function
Beisel CL, Smolke CD (2009)
PLOS Computational Biology, 5 (4): 10003
2008
Model-guided design of ligand-regulated RNAi for programmable control of gene expression
Beisel CL, Bayer TS, Hoff KG, Smolke CD (2008)
Molecular Systems Biology, 4: 224
2005
Conformational analysis of gossypol and its derivatives by molecular mechanics
Beisel CL, Dowd MK, Reilly PJ (2005)
Journal Of Molecular Structure: Computational and Theoretical Chemistry, 730 (1-3): 51-58
2002
Cochlear whole mount in situ hybridization: identification of longitudinal and radial gradients
Judice TN, Nelson NC, Beisel CL, Delimont DC, Fritzsch B, Beisel KW (2002)
Brain Research Protocols, 9 (1): 65-76