Prof. Chase Beisel
Biologie synthetischer RNA
Die Arbeitsgruppe von Chase Beisel arbeitet an der Schnittstelle von CRISPR-Biologie und -Technologien. Sie erforschen die funktionelle Vielfalt von CRISPR-Cas-Immunsystemen, um neue Technologien zu entwickeln, die zum besseren Verständnis, zur Diagnose und zur Behandlung von Infektionen des Menschen eingesetzt werden können.
Unsere Forschung
Die Entdeckung der CRISPR-Cas-Immunsysteme in Mikroorganismen hat zur Entwicklung revolutionärer Werkzeuge zur Genom-Editierung und vieler anderen Anwendungen mit gesellschaftlichem Nutzen geführt. In der Infektionsbiologie können CRISPR-Werkzeuge zur Untersuchung von Krankheitserregern, der Mikrobiota und menschlichen Zellen, aber auch zur Diagnose und Behandlung von Infektionen eingesetzt werden.
Chase Beisels Team nutzt den Ansatz der synthetischen Biologie, um zu untersuchen, wie diese Immunsysteme funktionieren und wie sie in Technologien umgewandelt werden können. Erforscht werden die Eigenschaften der Immunsysteme mit Hilfe von zellfreien Transkriptions-Translations-Systemen sowie E. coli und anderen Bakterien, die diese Systeme in sich tragen. Außerdem setzen die Forscher standardmäßig Hochdurchsatzverfahren wie Next-Generation-Sequencing und Bibliotheks-Screenings ein, um umfangreiche Informationen aus individuellen Experimenten zu sammeln.
Die Arbeitsgruppe hat bereits eine Reihe wichtiger CRISPR-basierter Technologien entwickelt und optimiert, einschließlich der Verwendung von CRISPR für Genom-Editierung und Genregulation in Bakterien, für Multi-Test-Diagnostika und für maßgeschneiderte antimikrobielle Wirkstoffe. Ihr Ziel ist es, CRISPR-Technologien zu nutzen, um unser Verständnis von menschlichen Infektionen zu vertiefen und diagnostische Werkzeuge zusammen mit maßgeschneiderten therapeutischen Ansätzen zu entwickeln.
Team-Mitglieder
Prof. Chase Beisel
Gruppenleiter
Ahsen Özcan
Postdoc
Dr. Daphne Collias
Postdoc
Dr. Ioannis Mougiakos
Postdoc
Dr. Oleg Dmytrenko
Postdoc
Adini Arifah
Doktorandin
Chunlei Jiao
Doktorand
Darshana Gupta
Doktorandin
Elena Vialetto
Doktorandin
Frank Englert
Doktorand
Franziska Wimmer
Doktorandin
Harris Bassett
Doktorand
Katharina Wandera
Doktorandin
Sandra Gawlitt
Doktorandin
Dr. Anzhela Migur
Technische Assistentin
Jiaqi Yu
Technische Assistentin
Jimmy Jeske
Technischer Assistent
Tatjana Achmedov
Technische Assistentin
Forschungsprojekte
CRISPR-Entdeckung aus Würzburg bereitet Weg für neuartiges Corona-Testverfahren:
Bin ich mit SARS-CoV-2 infiziert? Handelt es sich um das Ursprungsvirus oder eine gefährlichere Mutante? Diese und mehr Fragen mit einem einzigen effizienten Testverfahren beantworten zu können, kann für den weiteren Krankheitsverlauf und die Therapie entscheidend sein. Würzburger Forscher:innen des Helmholtz-Instituts für RNA-basierte Infektionsforschung und der Julius-Maximilians-Universität haben in einer im Magazin Science erschienenen Studie ihre neuen CRISPR-Erkenntnisse und die darauf basierende Diagnostiktechnologie LEOPARD vorgestellt.
Publikationen
2021
A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression
Taxiarchi C, Beaghton A, Don NI, Kyrou K, Gribble M, Shittu D, Collins SP, Beisel CL, Galizi R, Crisanti A (2021)
Nature Communications 12 (1): 3977
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
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
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
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