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Prof Chase Beisel

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

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

Characterization of Cas12a nucleases reveals diverse PAM profiles between closely-related orthologs

Jacobsen T, Ttofali F, Liao C, Manchalu S, Gray B, Beisel C (2020)

Nucleic Acids Research, 48 (10): 5624-5638

Tunable self-cleaving ribozymes for modulating gene expression in eukaryotic systems

Jacobsen T, Yi G, Al Asafen H, Jermusyk A, Beisel C, Reeves G (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 M, Bidstrup S, Vento J, Aunsbjerg S, Bosma E, McNair L, Beisel C, Neves A (2020)

Applied And Environmental Microbiology, 86 (7): 02312-19

Methods for characterizing, applying, and teaching CRISPR-Cas systems

Beisel C (2020)

Methods (San Diego, Calif.), 172: 1-2

CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers

Wimmer F, Beisel C (2020)

Frontiers In Microbiology, 10: 3078

2019

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)

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 R, Denny S, Cecil T, Leenay R, Keung A, Beisel C (2019)

Nature Communications, 10 (1): 2948

An educational module to explore CRISPR technologies with a cell-free transcription-translation system

Collias D, Marshall R, Collins S, Beisel C, Noireaux V (2019)

Synthetic Biology (Oxford, England), 4 (1): 156

Rapid Testing of CRISPR Nucleases and Guide RNAs in an E. coli Cell-Free Transcription-Translation System

Marshal R, Beisel C, Noireaux V (2019)

STAR Protocols

CRATES: A one-step assembly method for Class 2 CRISPR arrays

Liao C, Slotkowski R, Beisel C (2019)

Methods In Enzymology, 629: 493-511

Barriers to genome editing with CRISPR in bacteria

Vento J, Crook N, Beisel C (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 C, 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 C, Chappell J, Agrawal D, Dunlop M, Noireaux V, Beisel C, 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 K, Collins S, Wimmer F, Marshall R, Noireaux V, Beisel C (2019)

Methods (San Diego, Calif.), 172: 42-50

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): 085

2018

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): 109-119

CRISPR tool puts RNA on the record

Beisel C (2018)

Nature, 562 (7727): 347-349

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)

Molecular Cell, 69 (1): 146-157

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)

Molecular Cell, 69 (5): 893-905

Advances in CRISPR Technologies for Microbial Strain Engineering

Alper H, Beisel C (2018)

Biotechnology Journal, 13 (9): 18004

Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications

Bober J, Beisel C, Nair N (2018)

Annual Review Of Biomedical Engineering, 20: 277-300

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 Synthetic Biology, 7 (5): 1219-1228

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: 48-57

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)

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 R, Achmedov T, Beisel C (2018)

RNA Biology, 16 (4): 404-412

2017

Deciphering, Communicating, and Engineering the CRISPR PAM

Leenay R, Beisel C (2017)

Journal Of Molecular Biology, 429 (2): 177-191

Toward a genetic tool development pipeline for host-associated bacteria

Waller M, Bober J, Nair N, Beisel C (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 C, Collins S, Beisel C, Noireaux V (2017)

Biotechnology And Bioengineering, 114 (9): 2137-41

Advancing the design and delivery of CRISPR antimicrobials

Fagen J, Collias D, Singh A, Beisel C (2017)

Current Opinion In Biomedical Engineering, 4: 57-64

2016

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 Research, 44 (15): 7385-94

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)

Molecular Cell, 62 (1): 137-47

Synthetic Biology - Engineering Genes with CRISPR-Cas9

Luo M, Beisel C (2016)

CEP Magazine, September

Rethinking the Hierarchy of Sugar Utilization in Bacteria

Beisel C, Afroz T (2016)

Journal Of Bacteriology, 198 (3): 374-376

Current and future prospects for CRISPR-based tools in bacteria

Luo M, Leenay R, Beisel C (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 J, Hu Q, Wang C, Beisel C, Gu Z (2015)

Angewandte Chemie (International ed. in English), 54 (41): 12029-33

Trade-offs in engineering sugar utilization pathways for titratable control

Afroz T, Biliouris K, Boykin K, Kaznessis Y, Beisel C (2015)

ACS Synthetic Biology, 4 (2): 141-9

Impact of Residual Inducer on Titratable Expression Systems

Afroz T, Luo M, Beisel C (2015)

PloS one, 10 (9): 01374

Repurposing endogenous type I CRISPR-Cas systems for programmable gene repression

Luo M, Mullis A, Leenay R, Beisel C (2015)

Nucleic Acids Research, 43 (1): 674-81

2014

A CRISPR design for next-generation antimicrobials

Beisel C, Gomaa A, Barrangou R (2014)

Genome Biology, 15 (11): 516

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)

Molecular Cell, 56 (2): 333-339

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: 259-67

Bacterial sugar utilization gives rise to distinct single-cell behaviours

Afroz T, Biliouris K, Kaznessis Y, Beisel C (2014)

Molecular Microbiology, 93 (6): 1093-1103

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): 00928-13

2013

Understanding and exploiting feedback in synthetic biology

Afroz T, Beisel C (2013)

Chemical Engineering Science, 103: 79-90

2012

Multiple factors dictate target selection by Hfq-binding small RNAs

Beisel C, Updegrove T, Janson B, Storz G (2012)

The EMBO Journal, 31 (8): 1961-74

2010

Base pairing small RNAs and their roles in global regulatory networks

Beisel C, Storz G (2010)

FEMS Microbiology Reviews, 34 (5): 866-82

2009

Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

Bayer T, Hoff K, Beisel C, Lee J, Smolke C (2009)

Journal Of Biological Engineering, 3: 1

Design Principles for Riboswitch Function

Beisel C, Smolke C (2009)

PLoS Computational Biology, 5 (4): 10003

2008

Model-guided design of ligand-regulated RNAi for programmable control of gene expression

Beisel C, Bayer T, Hoff K, Smolke C (2008)

Molecular Systems Biology, 4: 224

2005

Conformational analysis of gossypol and its derivatives by molecular mechanics

Beisel C, Dowd M, Reilly P (2005)

Journal Of Molecular Structure: THEOCHEM, 730 (1-3): 51-58

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 Research Protocols, 9 (1): 65-76

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