Z03

Advanced genetic screens and genome engineering

Funding period: 2017-2029

Project Z03

Project Leaders

Prof. Dr. Michael Boutros

 Project Leader A01, Z01, Z03

Abstract

Platform Z03 provides access to advanced genome engineering methods and high-throughput screening technology for CRC 1324 members. In the last funding period, the project has generated in vitro and in vivo CRISPR models for loss-of-function studies and various knock-in lines. Z03 also developed novel genome editing approaches for mutagenesis and high-efficiency base editing. In the next funding period, Z03 will continue to provide CRC members with advanced genome engineering and screening capabilities, including new advances, such as characterization by long-read sequencing and precision genome engineering with prime- and base editing.

Project-related Publications

Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs

Port F, Buhmann MA, Zhou J, Stricker M, Vaughan-Brown A, Michalsen AC, Roßmanith E, Pöltl A, Großkurth L, Huber J, Menendez Kury LB, Weberbauer B, Hübl M, Puscher E, Heigwer F, Boutros M. Nat Commun. 2026 Jan 15;17(1):877. doi: 10.1038/s41467-026-68434-z.

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Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer

Haas A, Wenz F, Hattemer J, Wesslowski J, Davidson G, Voloshanenko O, Boutros M, Acebron SP, Bastians H. Life Sci Alliance. 2025 Aug 22;8(11):e202503295. doi: 10.26508/lsa.202503295. Print 2025 Nov. PMID: 40846632

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Combined MEK and PARP inhibition enhances radiation response in rectal cancer

Xiao Q, Riedesser JE, Mulholland T, Li Z, Buchloh J, Albrecht P, Yang X, Li M, Venkatachalam N, Skabkina O, Klupsch A, Eichhorn E, Wang L, Belle S, Schulte N, Schmitz D, Froelich MF, Trikhirhisthit K, Valentini E, Boonekamp KE, Petersen Y, Miersch T, Burgermeister E, Herskind C, Veldwijk MR, Brochhausen C, Ihnatko R, Krijgsveld J, Kurth I, Zhu Y, Ma Y, Cao K, Boutros M, Ebert MP, Zhan T, Betge J. Cell Rep Med. 2025 Aug 5:102284. doi: 10.1016/j.xcrm.2025.102284. Online ahead of print.

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WNT5a export onto extracellular vesicles studied at single-molecule and single-vesicle resolution

Schubert A, Mongkolsittisilp A, Kobitski A, Schulz M, Voloshanenko O, Schaffrinski M, Winkler N, Neßling M, Richter K, Kranz D, Nienhaus K, Jäger D, Trümper L, Büntzel J, Binder C, Nienhaus GU, Boutros M. FEBS J. 2025 Apr 1.

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A temperature-tolerant CRISPR base editor mediates highly efficient and precise gene editing in Drosophila

Doll RM, Boutros M, Port F. Sci Adv. 2023 Sep;9(35):eadj1568. doi: 10.1126/sciadv.adj1568. Epub 2023 Aug 30. PMID: 37647411

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The Roles of Secreted Wnt Ligands in Cancer

Werner J, Boonekamp KE, Zhan T, Boutros M. Int J Mol Sci. 2023 Mar 10;24(6):5349. doi: 10.3390/ijms24065349. PMID: 36982422

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The role of Evi/Wntless in exporting Wnt proteins

Wolf L, Boutros M. Development. 2023 Feb 15;150(3):dev201352. doi: 10.1242/dev.201352. Epub 2023 Feb 10.
PMID: 36763105

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Blockade of Wnt Secretion Attenuates Myocardial Ischemia-Reperfusion Injury by Modulating the Inflammatory Response

Meyer IS, Li X, Meyer C, Voloshanenko O, Pohl S, Boutros M, Katus HA, Frey N, Leuschner F. Int J Mol Sci. 2022 Oct 14;23(20):12252. doi: 10.3390/ijms232012252.
PMID: 36293109

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Tissue-Specific CRISPR-Cas9 Screening in Drosophila

Port F, Boutros M. Methods Mol Biol. 2022;2540:157-176. doi: 10.1007/978-1-0716-2541-5_7. PMID: 35980577

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Superresolution microscopy localizes endogenous Dvl2 to Wnt signaling-responsive biomolecular condensates

Schubert A, Voloshanenko O, Ragaller F, Gmach P, Kranz D, Scheeder C, Miersch T, Schulz M, Trümper L, Binder C, Lampe M, Engel U, Boutros M. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2122476119. doi: 10.1073/pnas.2122476119. Epub 2022 Jul 22. PMID: 35867833

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Allele-specific endogenous tagging and quantitative analysis of β-catenin in colorectal cancer cells

Ambrosi G, Voloshanenko O, Eckert AF, Kranz D, Nienhaus GU, Boutros M. Elife. 2022 Jan 11;11:e64498. doi: 10.7554/eLife.64498.
PMID: 35014953

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EVI/WLS function is regulated by ubiquitination and linked to ER-associated degradation by ERLIN2

Wolf LM, Lambert AM, Haenlin J, Boutros M. J Cell Sci. 2021 Jul 19:jcs.257790. doi: 10.1242/jcs.257790. Online ahead of print.
PMID: 3427964

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Wnt10b GSK3β dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

Lin YC, Haas A, Bufe A, Parbin S, Hennecke M, Voloshanenko O, Gross J, Boutros M, Acebron SP, Bastians H. Life Sci Alliance. 2020 Nov 30;4(1):e202000855. Print 2021 Jan.
PMID: 33257473

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Extracellular vesicles and oncogenic signaling

Schubert A, Boutros M. Mol Oncol. 2020 Nov 18. doi: 10.1002/1878-0261.12855. PMID: 33207034

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Multiplexed conditional genome editing with Cas12a in Drosophila

Port F, Starostecka M, Boutros M. Proc Natl Acad Sci U S A. 2020 Aug 25:202004655.

PMID: 32843348

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eGFP-tagged Wnt-3a enables functional analysis of Wnt trafficking and signaling and kinetic assessment of Wnt binding to full-length Frizzled

Wesslowski J, Kozielewicz P, Wang X, Cui H, Schihada H, Kranz D, Karuna M P, Levkin P, Gross JC, Boutros M, Schulte G, Davidson G. J Biol Chem. 2020 May 7. pii: jbc.RA120.012892. PMID:32381507

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gscreend: modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection

Imkeller K, Ambrosi G, Boutros M, Huber W. Genome Biol. 2020 Mar 2; 21(1):53. PMID: 32122365

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A Large-Scale Resource for Tissue-Specific CRISPR Mutagenesis in Drosophila

Port F, Strein C, Stricker M, Rauscher B, Heigwer F, Zhou J, Beyersdörffer C, Frei J, Hess A, Kern K, Lange L, Langner N, Malamud R, Pavlović B, Rädecke K, Schmitt L, Voos L, Valentini E, Boutros M. Elife. 2020 Feb 13;9:e53865.

PMID: 32053108

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Exocyst-mediated apical Wg secretion activates signaling in the Drosophila wing epithelium

Chaudhary V, Boutros M. PLoS Genet. 2019 Sep 17;15(9):e1008351. PMID: 31527874

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Toward an integrated map of genetic interactions in cancer cells

Rauscher B, Heigwer F, Henkel L, Hielscher T, Voloshanenko O, Boutros M. Mol Syst Biol. 2018 Feb 21;14(2):e7656. doi: 10.15252/msb.20177656. PMID: 29467179

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β-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells

Voloshanenko O, Schwartz U, Kranz D, Rauscher B, Linnebacher M, Augustin I, Boutros M. Sci Rep. 2018 Feb 16;8(1):3178. PMID:29453334

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ERAD-dependent control of the Wnt secretory factor Evi

Glaeser K, Urban M, Fenech E, Voloshanenko O, Kranz D, Lari F, Christianson JC, Boutros M. EMBO J. 2018 Feb 15;37(4). PMID:29378775  

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Mapping of Wnt-Frizzled interactions by multiplex CRISPR targeting of receptor gene families

Voloshanenko O, Gmach P, Winter J, Kranz D, Boutros M. FASEB J. 2017 Nov;31(11):4832-4844. doi: 10.1096/fj.201700144R. Epub 2017 Jul 21. PMID: 28733458

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Secretion of Wnt ligands requires Evi, a conserved transmembrane protein

Bartscherer K, Pelte N, Ingelfinger D, Boutros M. Cell. 2006 May 5;125(3):523-33. doi: 10.1016/j.cell.2006.04.009. PMID: 16678096

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