High-Content CRISPR Screens (HCCS)

Service

• 500 DKK/hour Academic
• 1000 DKK/hour Industrial

Instrument usage

Libraries

Genome wide human single guide RNA (sgRNA) library from Horizon targeting 19035 genes 

Cherry picked customized sublibraries can be purchased in 384-well format.

The facility offers assay readout and liquid handling.

Microscopes 

Plate readers 

Automated Liquid Handling

Flow Cytometry

Here you can read publications from the facility

Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models. Metrangolo, V., Hansen Blomquist, M., Dutta, A., Gårdsvoll, H., Krigslund, O., Nørregaard, K. S., Jürgensen, H. J., Ploug, M., Flick, M. J., Behrendt, N., and Engelholm, L. H. (2025) 'Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models', Sci Adv, 11(3), pp. eadq0513. https://doi.org/10.1126/sciadv.adq0513

A synthetic lethal dependency on casein kinase 2 in response to replication-perturbing therapeutics in RB1-deficient cancer cells. Bulanova, D., Akimov, Y., Senkowski, W., Oikkonen, J., Gall-Mas, L., Timonen, S., Elmadani, M., Hynninen, J., Hautaniemi, S., Aittokallio, T. and Wennerberg, K. (2024) 'A synthetic lethal dependency on casein kinase 2 in response to replication-perturbing therapeutics in RB1-deficient cancer cells', Sci Adv, 10(21), pp. eadj1564. https://doi.org/10.1126/sciadv.adj1564

Single-cell transcriptomes identify patient-tailored therapies for selective co-inhibition of cancer clones. Ianevski, A., Nader, K., Driva, K., Senkowski, W., Bulanova, D., Moyano-Galceran, L., Ruokoranta, T., Kuusanmaki, H., Ikonen, N., Sergeev, P., Vaha-Koskela, M., Giri, A. K., Vaharautio, A., Kontro, M., Porkka, K., Pitkanen, E., Heckman, C. A., Wennerberg, K. and Aittokallio, T. (2024) 'Single-cell transcriptomes identify patient-tailored therapies for selective co-inhibition of cancer clones', Nat Commun, 15(1), pp. 8579. https://doi.org/10.1038/s41467-024-52980-5

Synthetic lethal interaction between WEE1 and PKMYT1 is a target for multiple low-dose treatment of high-grade serous ovarian carcinoma. Benada, J., Bulanova, D., Azzoni, V., Petrosius, V., Ghazanfar, S., Wennerberg, K. and Sorensen, C. S. (2023) 'Synthetic lethal interaction between WEE1 and PKMYT1 is a target for multiple low-dose treatment of high-grade serous ovarian carcinoma', NAR Cancer, 5(3), pp. zcad029.  https://doi.org/10.1093/narcan/zcad029

A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids. Senkowski, W., Gall-Mas, L., Falco, M. M., Li, Y., Lavikka, K., Kriegbaum, M. C., Oikkonen, J., Bulanova, D., Pietras, E. J., Voßgröne, K., Chen, Y. J., Erkan, E. P., Dai, J., Lundgren, A., Grønning Høg, M. K., Larsen, I. M., Lamminen, T., Kaipio, K., Huvila, J., ... Wennerberg, K. (2023). A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids. Developmental Cell, 58(12), 1106-1121.e7. https://doi.org/10.1016/j.devcel.2023.04.012

The Irradiated Brain Microenvironment Supports Glioma Stemness and Survival via Astrocyte-Derived Transglutaminase 2. Berg TJ, Marques C, Pantazopoulou V, Johansson E, von Stedingk K, Lindgren D, Jeannot P, Pietras EJ, Bergström T, Swartling FJ, Governa V, Bengzon J, Belting M, Axelson H, Squatrito M, Pietras A.Cancer Res. 2021 Apr 15;81(8):2101-2115. doi: 10.1158/0008-5472.CAN-20-1785. Epub 2021 Jan 22.PMID: 33483373

A high-throughput screen identifies the long non-coding RNA DRAIC as a regulator of autophagy. Tiessen I, Abildgaard MH, Lubas M, Gylling HM, Steinhauer C, Pietras EJ, Diederichs S, Frankel LB, Lund AH. Oncogene. 2019 Mar 14. doi: 10.1038/s41388-019-0783-9. [Epub ahead of print]

eIF5A is required for autophagy by mediating ATG3 translation. Lubas M, Harder LM, Kumsta C, Tiessen I, Hansen M, Andersen JS, Lund AH, Frankel LB. EMBO Rep. 2018 Jun;19(6). pii: e46072. doi: 10.15252/embr.201846072. Epub 2018 Apr 30.

Structure-Based Design of a New Scaffold for Cell-Penetrating Peptidic Inhibitors of the Histone Demethylase PHF8. Dorosz J, Olsen L, Seger ST, Steinhauer C, Bouras G, Helgstrand C, Wiuf A, Gajhede M. Chembiochem. 2017 Jul 18;18(14):1369-1375. doi: 10.1002/cbic.201700109. Epub 2017 Jun 13.

CD44 Interacts with HIF-2 to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells. Johansson, Elinn; Grassi, Elisa S.; Pantazopoulou, Vasiliki; Tong, Bei; Lindgren, David; Berg, Tracy J.; Pietras, Elin Josefina; Axelson, Håkan; Pietras, Alexander. Cell Reports. 15 August 2017 Volume 20, Issue 7, Pages 1641-1653. https://doi.org/10.1016/j.celrep.2017.07.049

High-throughput siRNA screening applied to the ubiquitin-proteasome system. Poulsen EG, Nielsen SV, Pietras EJ, Johansen JV, Steinhauer C and Hartmann-Petersen R Methods in Molecular Biology: Proteostasis 2016; 1449:421-39

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control. Klein DK, Hoffmann S, Ahlskog JK, O'Hanlon K, Quaas M, Larsen BD, Rolland B, Rösner HI, Walter D, Kousholt AN, Menzel T, Lees M, Johansen JV, Rappsilber J, Engeland K, Sørensen CS. Nat Commun. 2015 Jan 5;6:5800. doi: 10.1038/ncomms6800.

miR-339-5p regulates the p53 tumor-suppressor pathway by targeting MDM2. Jansson MD, Damas ND, Lees M, Jacobsen A, Lund AH.Oncogene. 2014 Jun 2. doi: 10.1038/onc.2014.130. [Epub ahead of print]

New histone supply regulates replication fork speed and PCNA unloading. Mejlvang J, Feng Y, Alabert C, Neelsen KJ, Jasencakova Z, Zhao X, Lees M, Sandelin A, Pasero P, Lopes M, Groth A. J Cell Biol. 2014 Jan 6;204(1):29-43. doi: 10.1083/jcb.201305017. Epub 2013 Dec 30.

A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence. Kooistra SM, Nørgaard LC, Lees MJ, Steinhauer C, Johansen JV, Helin K. PLoS One. 2014 Mar 20;9(3):e91034. doi: 10.1371/journal.pone.0091034. eCollection 2014.

Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation. Malatesta M, Steinhauer C, Mohammad F, Pandey DP, Squartrito M, Helin K. (2013) Cancer Res. 2013 Aug 13. [Epub ahead of print]

A loss-of-function screen for phosphatases that regulate neurite outgrowth identifies PTPN12 as a negative regulator of TrkB tyrosine phosphorylation. Ambjørn M, Dubreuil V, Miozzo F, Nigon F, Møller B, Issazadeh-Navikas S, Berg J, Lees M, Sap J. (2013). PLoS One. 2013 Jun 13;8(6):e65371. doi: 10.1371/journal.pone.0065371. Print 2013.

IFNB1/interferon-β-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function. Ambjørn M, Ejlerskov P, Liu Y, Lees M, Jäättelä M, Issazadeh-Navikas S. Autophagy. 2012 Dec 7;9(3).

HUWE1 and TRIP12 Collaborate in Degradation of Ubiquitin-Fusion Proteins and Misframed Ubiquitin. Poulsen EG, Steinhauer C, Lees M, Lauridsen AM, Ellgaard L, Hartmann-Petersen R. PLoS One. 2012;7(11):e50548. doi: 10.1371/journal.pone.0050548. Epub 2012 Nov 27.

Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor. Kristensen LH, Nielsen AL, Helgstrand C, Lees M, Cloos P, Kastrup JS, Helin K, Olsen L, Gajhede M. FEBS J. 2012 Jun;279(11):1905-14. doi: 10.1111/j.1742-4658.2012.08567.x. Epub 2012 May 2.

Identification of catechols as histone-lysine demethylase inhibitors. Nielsen AL, Kristensen LH, Stephansen KB, Kristensen JB, Helgstrand C, Lees M, Cloos P, Helin K, Gajhede M, Olsen L. FEBS Lett. 2012 Apr 24;586(8):1190-4. Epub 2012 Mar 15.

microRNA-101 is a potent inhibitor of autophagy. Frankel LB, Wen J, Lees M, Høyer-Hansen M, Farkas T, Krogh A, Jäättelä M, Lund AH. EMBO J. 2011 Sep 13. doi: 10.1038/emboj.2011.331 .

A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance. Menzel T, Nähse-Kumpf V, Kousholt AN, Klein DK, Lund-Andersen C, Lees M, Johansen JV, Syljuåsen RG, Sørensen CS. EMBO Rep. 2011 Jul 1;12(7):705-12. doi: 10.1038/embor.2011.99.

Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. Beck H, Nähse V, Larsen MS, Groth P, Clancy T, Lees M, Jørgensen M, Helleday T, Syljuåsen RG, Sørensen CS. J Cell Biol. 2010 Mar 8;188(5):629-38. Epub 2010 Mar 1.

p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Christoffersen NR, Shalgi R, Frankel LB, Leucci E, Lees M, Klausen M, Pilpel Y, Nielsen FC, Oren M, and A. H. Lund. (2010). Cell Death and Differentiation 17:236-45.

We engage in collaboration with the DK-OPENSCREEN facility at DTU, offering users access to a broad range of chemical screening approaches and large drug-like chemical collections. Read more about DK-OPENSCREEN here.

For pooled CRISPR screens and the creation of Cas-expressing cell lines, please reach out to CRISPR Functional Genomics at SciLifeLab.

Additionally, we are affiliated with the Danish BioImaging network (read more about Danish Biolmaging network here) alongside CFIM (Copenhagen Center for Fluorescence Microscopy, read more about CFIM here) and DBI-INFRA (Danish Bioimaging Infrastructure, visit DBI-INFRA website through this link).

 We receive support from an advisory board consisting of:

• Eric Paul Bennet, Specialist, Biopharm Department for Gene Therapy, Novo Nordisk
• Jordi Carreras Puigvert, Lecturer, Department of Pharmaceutical Biosciences; Research; Pharmaceutical Bioinformatics, Uppsala University
• Davide Gianni, Senior Director, Functional Genomics, Discovery Sciences, R&D, AstraZeneca
• Robin Ketteler, Professor of Biochemistry, Head of Department of Human Medicine, Medical School Berlin
• Carolina Wählby, Professor at Department of Information Technology, Uppsala University

Novel high-throughput CRISPR-Select using 96-well cell culture robotics

We have helped develop a streamlined and automated pipeline for analysis of CRISPR-engineered genetic variants (mutations) found in patients in e.g. cancer predisposition genes.

This approach utilizes robotics to manage drug delivery, monitor cell growth, split cell cultures at appropriate cell densities and refresh cell cultures efficiently.

This innovative system not only significantly reduces the time and labor required for analysis, but also enables the investigation of thousands of variants of uncertain significance for cancer relevance with unparalleled precision.

This represents a major leap forward in genetic research, offering promising opportunities for cancer prevention and treatment.

Precision Targets in Glioblastoma Therapy

This project focuses on identifying and validating new therapeutic targets for glioblastoma (GBM), particularly targeting the glioblastoma stem cells (GSCs) responsible for tumor growth and recurrence.

By employing automated high-throughput CRISPR screening (by validating 1239 putative GSC-specific gene dependencies) and patient-derived neurosphere models, we aim to help our user to uncover genes critical to GSC survival and assess their viability as targets for precision medicine.

This streamlined methodology facilitates the rapid discovery of genetic vulnerabilities and the efficient testing of potential therapeutic drugs, paving the way for the development of more effective, personalized GBM treatments.

The HCCS facility now has a compound/drug storage system. Users can:

• Request aliquots of compounds for testing
• Request the creation of ready to use drug plates
• Store their valuable compounds in a controlled atmosphere pod

Contact the HCCS (hccs@bric.ku.dk) to get a current list of compounds and pricing for your needs.

Read more about the storage system on this website.