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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

Chunlei Jiao

Chunlei Jiao

PhD Student

Daphne Collias

Daphne Collias

PhD Student

Elena Vialetto

Elena Vialetto

PhD Student

Sandra Gawlitt

Sandra Gawlitt

PhD Student

Jiaqi Yu

Jiaqi Yu

Technical Assistant

Tatjana Achmedov

Tatjana Achmedov

Technical Assistant

Frank Englert

Frank Englert

Master Student

Natalia Luise Peeck

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

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 MicrobiologyDOI: 10.1128/AEM.02312-19

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)

Frontiers In Microbiology, 10: 1365DOI: 10.3389/fmicb.2019.03078

2019

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): 156DOI: 10.1093/synbio/ysz005

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

Marshal R, Beisel, Chase L., Noireaux, Vincent (2019)

STAR Protocols

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 BiotechnologyDOI: 10.1038/s41587-019-0235-7

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

Liao C, Slotkowski R, Beisel C (2019)

Methods In Enzymology, 629: 493-511DOI: 10.1016/bs.mie.2019.04.011

Barriers to genome editing with CRISPR in bacteria

Vento J, Crook N, Beisel C (2019)

Journal Of Industrial Microbiology & Biotechnology, 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

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)

Biotechnology And Bioengineering, 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

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

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

CRISPR tool puts RNA on the record

Beisel C (2018)

Nature, 562 (7727): 347-349DOI: 10.1038/d41586-018-06869-1

Advances in CRISPR Technologies for Microbial Strain Engineering

Alper H, Beisel C (2018)

Biotechnology Journal, 13 (9): 18004DOI: 10.1002/biot.201800460

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: 277-300DOI: 10.1146/annurev-bioeng-062117-121019

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): 1219-1228DOI: 10.1021/acssynbio.8b00040

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

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): 17005DOI: 10.1002/biot.201700583

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

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): 146-157DOI: 10.1016/j.molcel.2017.12.007

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): 893-905DOI: 10.1016/j.molcel.2018.01.032

2017

What Is the Role of Circuit Design in the Advancement of Synthetic Biology? Part 1

Beisel C (2017)

Cell Systems, 4 (4): 370-372DOI: 10.1016/j.cels.2017.04.003

Deciphering, Communicating, and Engineering the CRISPR PAM

Leenay R, Beisel C (2017)

Journal Of Molecular Biology, 429 (2): 177-191DOI: 10.1016/j.jmb.2016.11.024

Toward a genetic tool development pipeline for host-associated bacteria

Waller M, Bober J, Nair N, Beisel C (2017)

Current Opinion In Microbiology, 38: 156-164DOI: 10.1016/j.mib.2017.05.006

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): 2137-41DOI: 10.1002/bit.26333

Advancing the design and delivery of CRISPR antimicrobials

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

Current Opinion In Biomedical Engineering, 4: 57-64DOI: 10.1016/j.cobme.2017.10.001

2016

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): 374-376DOI: 10.1128/JB.00890-15

Current and future prospects for CRISPR-based tools in bacteria

Luo M, Leenay R, Beisel C (2016)

Biotechnology And Bioengineering, 113 (5): 930-43DOI: 10.1002/bit.25851

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): 7385-94DOI: 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)

Molecular Cell, 62 (1): 137-47DOI: 10.1016/j.molcel.2016.02.031

2015

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): 141-9DOI: 10.1021/sb400162z

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

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): 12029-33DOI: 10.1002/anie.201506030

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): 674-81DOI: 10.1093/nar/gku971

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

A CRISPR design for next-generation antimicrobials

Beisel C, Gomaa A, Barrangou R (2014)

Genome Biology, 15 (11): 516DOI: 10.1186/s13059-014-0516-x

Bacterial sugar utilization gives rise to distinct single-cell behaviours

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

Molecular Microbiology, 93 (6): 1093-1103DOI: 10.1111/mmi.12695

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): 333-339DOI: 10.1016/j.molcel.2014.09.019

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

2013

Understanding and exploiting feedback in synthetic biology

Afroz T, Beisel C (2013)

Chemical Engineering Science, 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)

The EMBO Journal, 31 (8): 1961-74DOI: 10.1038/emboj.2012.52

2011

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 Research, 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)

Molecular Cell, 41 (3): 286-97DOI: 10.1016/j.molcel.2010.12.027

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

2010

Base pairing small RNAs and their roles in global regulatory networks

Beisel C, Storz G (2010)

FEMS Microbiology Reviews, 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)

Journal Of Biological Engineering, 3: 1DOI: 10.1186/1754-1611-3-1

Design Principles for Riboswitch Function

Beisel C, Smolke C (2009)

PLoS Computational Biology, 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)

Molecular Systems Biology, 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)

Journal Of Molecular Structure: 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 Research Protocols, 9 (1): 65-76DOI: 10.1016/S1385-299X(01)00138-6

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