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Prof Chase Beisel

RNA Synthetic Biology

The research group led by Chase Beisel works at the interface of CRISPR biology and technologies. They investigate the functional diversity of CRISPR-Cas immune systems to develop new technologies that can be employed to better understand, diagnose and treat human infections.

Our research and approach

The discovery of CRISPR-Cas immune systems in microbes has led to the development of revolutionary tools for genome editing and many other applications benefiting society. In infection biology, CRISPR tools can be used to interrogate pathogens, microbiota and human cells as well as to diagnose and treat infections.

Chase Beisel’s group adopts synthetic biology approaches to investigate how these immune systems function and how they can be converted into different technologies. They interrogate the properties of the immune systems using cell-free transcription-translation systems as well as E. coli and non-model bacteria naturally harboring these systems. They also regularly employ high-throughput approaches such as next-generation sequencing and library screening to collect extensive information from individual experiments.

The group has developed and advanced a number of important CRISPR-based technologies, including the use of CRISPR for genome editing and gene regulation in bacteria, for multi-test diagnostics, and for tailored-spectrum antimicrobials. Their overarching goal is to exploit CRISPR technologies to advance our understanding of human infections and develop diagnostic tools together with tailored therapeutic approaches.

Team members

Chase Beisel

Prof Chase Beisel

Group Leader

Adini Arifah

Adini Arifah

PhD Student

Chunlei Jiao

Chunlei Jiao

PhD Student

Darshana Gupta

Darshana Gupta

PhD Student

Elena Vialetto

Elena Vialetto

PhD Student

Frank Englert

Frank Englert

PhD Student

Franziska Wimmer

Franziska Wimmer

PhD Student

Harris Bassett

Harris Bassett

PhD Student

Sandra Gawlitt

Sandra Gawlitt

PhD Student

Anzhela Migur

Dr Anzhela Migur

Technical Assistant

Jiaqi Yu

Jiaqi Yu

Technical Assistant

Tatjana Achmedov

Tatjana Achmedov

Technical Assistant

Natalia Luise Peeck

Natalia Luise Peeck

Master Student

Research projects

CRISPR discovery from Würzburg paves the way for novel COVID testing method:

Am I infected with SARS-CoV-2? Is it one of the dangerous variants? Being able to answer these and more questions with a single efficient diagnostic test can be decisive for gauging the spread of disease and selecting the right therapy. In a study published in the journal Science, researchers from Würzburg at the Helmholtz Institute for RNA-based Infection Research and the Julius Maximilians University tackle this challenge with a new CRISPR discovery they translated into a diagnostic platform called LEOPARD.

Learn more

Publications

2021

CRISPR transposons on the move

Mougiakos I, Beisel CL (2021)

Cell Host & Microbe 29 (5): 675-677

Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9

Jiao C, Sharma S, Dugar G, Peeck NL, Bischler T, Wimmer F, Yu Y, Barquist L, Schoen C, Kurzai O, Sharma CM, Beisel CL (2021)

Science 372 (6545): 941-948

Sequence-independent RNA sensing and DNA targeting by a split domain CRISPR-Cas12a gRNA switch

Collins SP, Rostain W, Liao C, Beisel CL (2021)

Nucleic Acids Research 49 (5): 2985-2999

CRISPR technologies and the search for the PAM-free nuclease

Collias D, Beisel CL (2021)

Nature Communications 12: 555

In Situ Biomanufacturing of Small Molecules in the Mammalian Gut by Probiotic Saccharomyces boulardii

Durmusoglu D, Al'Abri IS, Collins SP, Cheng J, Eroglu A, Beisel CL, Crook N (2021)

ACS Synthetic Biology 10 (5): 1039-1052

A Code of Ethics for Gene Drive Research

Annas GJ, Beisel CL, Clement K, Crisanti A, Francis S, Galardini M, Galizi R, Grünewald J, Immobile G, Khalil AS, …, Taxiarchi C, Joung JK (2021)

The CRISPR journal 4 (1): 19-24

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

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

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

CRISPR tool puts RNA on the record

Beisel CL (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 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

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

SBE Supplement: Synthetic Biology – Engineering Genes with CRISPR-Cas9

Luo ML, Beisel CL (2016)

American Institute of Chemical Engineers

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

Self‐Assembled DNA Nanoclews for the Efficient Delivery of CRISPR–Cas9 for Genome Editing

Sun W, Ji W, Hall JM, Hu Q, Wang C, Beisel CL, Gu Z (2015)

Angewandte Chemie International Edition 54 (41): 12029-33

Integrative, ligand-responsive microRNAs

Smolke CD, Beisel CL (2015)

Patent (US9145555B2)

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

Modular polynucleotides for ligand-controlled regulatory systems

Smolke CD, Win MN, Beisel CL (2013)

Patent (US8367815B2)

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

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