Applications & Publications
Technical Notes
3D Tomographic Visualization of Zebrafish Larvae Using the VAST BioImager™ (QTN-026)
March 13, 2020
High-Throughput Craniofacial Development Phenotyping in Zebrafish using VAST BioImager (QTN-024)
January 04, 2017
D. rerio Analysis and Sorting: High throughput screening of innate immune responses in zebrafish embryos
Profiling of live D. reriolarvae using the COPAS XL instrument. Work performed in collaboration with the Spaink Laboratory, University of Leiden (ANXL-02)
Zebra Fish Sorting: Live embryos vs. Dead eggs
Automated Detection and Sorting of live D. rerio embryos from dead D. rerio eggs using the COPAS XL instrument (ANXL-01)
Publications
The zebrafish embryo as a model for chemically-induced steatosis: A case study with three pesticides
Heusinkveld et al. August 14, 2024 Toxicology,Volume 508,2024,153927,ISSN 0300-483X,https://doi.org/10.1016/j.tox.2024.153927.(https://www.sciencedirect.com/science/article/pii/S0300483X24002087)
The zebrafish embryo as a model for chemically-induced steatosis: A case study with three pesticides
In vivo multiscale analyses of spring viremia of carp virus (SVCV) infection: From model organism to target species
Souto et al. August 05, 2024 https://doi.org/10.1371/journal.ppat.1012328
In vivo multiscale analyses of spring viremia of carp virus (SVCV) infection: From model organism to target species
Adaptive Optics in an Oblique Plane Microscope
McFadden et al. March 22, 2024 bioRxiv 2024.03.21.586191; doi: https://doi.org/10.1101/2024.03.21.586191
Adaptive Optics in an Oblique Plane Microscope
Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy
Oprisoreanu et al. April 26, 2021 Dis Model Mech (2021) 14 (4): dmm047761. https://doi.org/10.1242/dmm.047761
Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy
Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform
Colón-Rodríguez A, et al. November 23, 2020 Front. Cell Dev. Biol. 8:586296.; doi: 10.3389/fcell.2020.586296
Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform
Morphometric analysis of developing zebrafish embryos allow predicting teratogenicity modes of action in higher vertebrates
Jarque et al. August 19, 2020 Reproductive Toxicology 96 (2020) 337-348; https://doi.org/10.1016/j.reprotox.2020.08.004
Morphometric analysis of developing zebrafish embryos allow predicting teratogenicity modes of action in higher vertebrates
The identification of dual protective agents against cisplatin-induced oto-and nephrotoxicity using the zebrafish model
Wertman JN, Melong N, Stoyek MR, et al. July 28, 2020 [published online ahead of print, 2020 Jul 28]. Elife. 2020;9:e56235. doi:10.7554/eLife.56235
The identification of dual protective agents against cisplatin-induced oto-and nephrotoxicity using the zebrafish model
Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/ Cas9-based approach
von der Heyde et al. July 16, 2020 Sci Rep 10, 11831 (2020). https://doi.org/10.1038/s41598-020-68567-1
Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/ Cas9-based approach
TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci
Davis et al. July 03, 2020 Human Molecular Genetics, , ddaa120, https://doi.org/10.1093/hmg/ddaa120
TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci
Integrative discovery of treatments for high-risk neuroblastoma
Almstedt et al. January 03, 2020 Nat Commun. 2020 Jan 3;11(1):71. doi: 10.1038/s41467-019-13817-8.
Integrative discovery of treatments for high-risk neuroblastoma
The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension
Morikawa et al. November 12, 2019 Science Signaling 12 Nov 2019: Vol. 12, Issue 607, eaay4430 DOI: 10.1126/scisignal.aay4430
The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension
Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans
Sylvia Dyballa et al. October 01, 2019 Toxicological Sciences, Volume 171, Issue 2, October 2019, Pages 283–295, https://doi.org/10.1093/toxsci/kfz165
Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans
TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish
Gudmundsson et al. September 01, 2019 Sci Rep. 2019; 9: 10730. Published online 2019 Jul 24. doi: 10.1038/s41598-019-46632-8
TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish
Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
Bandaru et al. June 11, 2019 bioRxiv 502674; doi: https://doi.org/10.1101/502674
Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features
Ansar et al. May 09, 2019 https://doi.org/10.1016/j.ajhg.2019.04.002
Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos’
Jarque et al. August 29, 2018 PLOS ONE | https://doi.org/10.1371/journal.pone.0203087 August 29, 2018
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos’
An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination
Early et al. July 06, 2018 DOI: 10.7554/eLife.35136 DOI: 10.7554/eLife.35136
An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination
Three-dimensional reconstruction and measurements of zebrafish larvae from high-throughput axial-view in vivo imaging
Guo et al. April 26, 2017 https://doi.org/10.1364/BOE.8.002611; Received 9 Nov 2016; revised 31 Jan 2017; accepted 31 Jan 2017; published 26 Apr 2017
Three-dimensional reconstruction and measurements of zebrafish larvae from high-throughput axial-view in vivo imaging
A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis.
Frosk et al. March 06, 2017 J Med Genet. 2017 Mar 6. pii: jmedgenet-2016-104296. doi: 10.1136/jmedgenet-2016-104296. [Epub ahead of print]
A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis.
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
Shaw et al. January 09, 2017 Nature Genetics (2017) doi:10.1038/ng.3743
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder
Kury et al. January 03, 2017 http://dx.doi.org/10.1016/j.ajhg.2017.01.003
De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder
ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian & Jeff S Mumm November 10, 2016 Nature Protocols 11, 2432–2453 (2016) doi:10.1038/nprot.2016.142
ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates
Developing systems for high-throughput screening of infectious diseases using zebrafish
Veneman, Wouter Jurjen December 05, 2015 Department of Animal Sciences and Health, Institute of Biology, Faculty of Science, Leiden University
Developing systems for high-throughput screening of infectious diseases using zebrafish
Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.
Mala Isrie 1,2 et al. October 14, 2015 Am J Hum Genet. 2015 Dec 3;97(6):790-800. doi: 10.1016/j.ajhg.2015.10.014.
View AbstractMutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.
1Center for Human Genetics, University Hospitals Leuven, 3000 Leuven, Belgium; 2Laboratory for Genetics of Cognition, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium
First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic ß-cell mass
Wang et al. July 28, 2015 eLife. 2015; 4: e08261. Published online 2015 Jul 28. doi: 10.7554/eLife.08261
First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic ß-cell mass
Semi-automated detection of goitrogenic compounds using transgenic zebrafish embryos and the VAST BioImager platform
SETAC Europe 25th Annual Meeting
Sergio Jarque¹, Eva Fetter², Marek Pípal¹, Marie Smutná¹, Ludek Blaha¹, Stefan Scholz².
May 03, 2015
Semi-automated detection of goitrogenic compounds using transgenic zebrafish embryos and the VAST BioImager platform
1RECETOX, Masaryk University, Faculty of Science, Kamenice 753/5, 625 00, Brno
2Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research – UFZ, Permoserstraße 15, 04318 Leipzig, Germany
Establishment and optimization of a high throughput setup to study Staphylococcus epidermidis and Mycobacterium marinum infection as a model for drug discovery.
Veneman WJ¹, Marín-Juez R², de Sonneville J³, Ordas A4, Jong-Raadsen S², Meijer AH4, Spaink HP5. June 26, 2014 JOVE
View AbstractEstablishment and optimization of a high throughput setup to study Staphylococcus epidermidis and Mycobacterium marinum infection as a model for drug discovery.
1Institute of Biology, Leiden University; w.j.veneman@biology.leidenuniv.nl. 2ZF-screens BV. 3Life Science Methods BV. 4Institute of Biology, Leiden University. 5Institute of Biology, Leiden University
Robotic injection of zebrafish embryos for high-throughput screening in disease models
Herman P. Spainka, Chao Cuib, Malgorzata I. Wiwegera, b, Hans J. Jansenb, Wouter J. Venemana, Rubén Marín-Juezb, Jan de Sonnevillec, Anita Ordasa, Vincenzo Torracaa, Wietske van der Enta, William P. Leendersd, Annemarie H. Meijer,a, B. Ewa Snaar-Jagalskaa, Ron P. Dirksb, August 15, 2013 Volume 62, Issue 3, 15 August 2013, Methods 62: 246–254
View AbstractRobotic injection of zebrafish embryos for high-throughput screening in disease models
a Department of Molecular Cell Biology, Institute of Biology, Leiden University, The Netherlands, b ZF-screens B.V., Leiden, The Netherlands, c Life Science Methods B.V., Leiden, The Netherlands, d Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
A zebrafish high throughput screening system used for Staphylococcus epidermidis infection marker discovery
Wouter J Veneman, Oliver W Stockhammer, Leonie de Boer, Sebastian A Zaat, Annemarie H Meijer and Herman P Spaink April 15, 2013 BMC Genomics 2013, 14:255 doi:10.1186/1471-2164-14-255
View AbstractA zebrafish high throughput screening system used for Staphylococcus epidermidis infection marker discovery
Background
Staphylococcus epidermidis bacteria are a major cause of biomaterial-associated infections in modern medicine. Yet there is little known about the host responses against this normally innocent bacterium in the context of infection of biomaterials. In order to better understand the factors involved in this process, a whole animal model with high throughput screening possibilities and markers for studying the host response to S. epidermidis infection are required.
Results
We have used a zebrafish yolk injection system to study bacterial proliferation and the host response in a time course experiment of S. epidermidis infection. By combining an automated microinjection system with complex object parametric analysis and sorting (COPAS) technology we have quantified bacterial proliferation. This system was used together with transcriptome analysis at several time points during the infection period. We show that bacterial colony forming unit (CFU) counting can be replaced by high throughput flow-based fluorescence analysis of embryos enabling high throughput readout. Comparison of the host transcriptome response to S. epidermidis and Mycobacterium marinum infection in the same system showed that M. marinum has a far stronger effect on host gene regulation than S. epidermidis. However, multiple genes responded differently to S. epidermidis infection than to M. marinum, including a cell adhesion gene linked to specific infection by staphylococci in mammals.
Conclusions
Our zebrafish embryo infection model allowed (i) quantitative assessment of bacterial proliferation, (ii) identification of zebrafish genes serving as markers for infection with the opportunistic pathogen S. epidermidis, and (iii) comparison of the transcriptome response of infection with S. epidermidis and with the pathogen M. marinum. As a result we have identified markers that can be used to distinguish common and specific responses to S. epidermidis. These markers enable the future integration of our high throughput screening technology with functional analyses of immune response genes and immune modulating factors.
High-throughput hyperdimensional vertebrate phenotyping
Carlos Pardo-Martin, Amin Allalou, Jaime Medina, Peter M. Eimon, Carolina Wählby Mehmet Fatih Yanik February 12, 2013 Nature Communications 4, Article number:1467, doi:10.1038/ncomms2475
High-throughput hyperdimensional vertebrate phenotyping
Presenting VAST BioImager™: A new modular, expandable platform to automate the orientation of 2-7 day old zebrafish larvae for imaging
The Nordic Countries Zebrafish Meeting on the Zebrafish as a model for Development and Disease
Union Biometrica, Geel, Belgium, Union Biometrica, Holliston, MA, USA
Yanik lab, MIT, Boston, MA, USA
November 21, 2012
Presenting VAST BioImager™: A new modular, expandable platform to automate the orientation of 2-7 day old zebrafish larvae for imaging
Development and Validation of an Automated High-Throughput System for Zebrafish In Vivo Screenings
Ainhoa Letamendia¹, Celia Quevedo¹, Izaskun Ibarbia¹, Juan M. Virto¹, Olaia Holgado¹, Maria Diez¹, Juan Carlos Izpisua Belmonte²,³, Carles Callol-Massot¹ May 15, 2012 PLoS ONE 7(5): e36690. doi:10.1371/journal.pone.0036690
View AbstractDevelopment and Validation of an Automated High-Throughput System for Zebrafish In Vivo Screenings
1Biobide S.L., San Sebastian, Guipuzcoa, Spain, 2Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America, 3Center of Regenerative Medicine in Barcelona, Barcelona, Spain
Fully automated cellular-resolution vertebrate screening platform with parallel animal processing
Chang TY, Pardo-Martin C, Allalou A, Wählby C, Yanik MF. February 01, 2012 Lab Chip. 2012 Feb 21;12(4):711-6. doi: 10.1039/c1lc20849g. Epub 2011 Dec 8.
Fully automated cellular-resolution vertebrate screening platform with parallel animal processing
A High-Throughput Screen for Tuberculosis Progression
Ralph Carvalho¹,³* Jan de Sonneville,² Oliver W. Stockhammer,³ Nigel D. L. Savage,4 Wouter J. Veneman,³ Tom H. M. Ottenhoff,4 Ron P. Dirks¹ Annemarie H. Meijer,³ and Herman P. Spaink ³ February 16, 2011 PLoS One. 2011; 6(2): e16779. 1) F-screens B.V., Leiden, The Netherlands, 2) Institute of Chemistry, Leiden University, Leiden, The Netherlands, 3) Institute of Biology, Leiden University, Leiden, The Netherlands,4) Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands
View AbstractA High-Throughput Screen for Tuberculosis Progression
One-third of the world population is infected with Mycobacterium tuberculosis and multi-drug resistant strains are rapidly evolving. The noticeable absence of a whole organism high-throughput screening system for studying the progression of tuberculosis is fast becoming the bottleneck in tuberculosis research. We successfully developed such a system using the zebrafish Mycobacterium marinum infection model, which is a well-characterized model for tuberculosis progression with biomedical significance, mimicking hallmarks of human tuberculosis pathology. Importantly, we demonstrate the suitability of our system to directly study M. tuberculosis, showing for the first time that the human pathogen can propagate in this vertebrate model, resulting in similar early disease symptoms to those observed upon M. marinum infection. Our system is capable of screening for disease progression via robotic yolk injection of early embryos and visual flow screening of late-stage larvae. We also show that this system can reliably recapitulate the standard caudal vein injection method with a throughput level of 2,000 embryos per hour. We additionally demonstrate the possibility of studying signal transduction leading to disease progression using reverse genetics at high-throughput levels. Importantly, we use reference compounds to validate our system in the testing of molecules that prevent tuberculosis progression, making it highly suited for investigating novel anti-tuberculosis compounds in vivo.
Zebrafish high throughput screening using robotic injection technology
The zebrafish embryo model in toxicology and teratology: Karlsruhe, Germany 2nd-3rd September 2010
Herman Spaink¹, Ron Dirks², Jan de Sonneville¹, Ralph Carvalho², Oliver Stockhammer¹,², Ewa Snaar-Jagalska¹, Annemarie Meijer¹
September 02, 2010
Zebrafish high throughput screening using robotic injection technology
1Leiden University, Leiden The Netherlands; 2ZF-screens B.V. Leiden, The Netherlands
High-throughput in vivo vertebrate screening.
Pardo-Martin C, Chang TY, Koo BK, Gilleland CL, Wasserman SC, Yanik MF. August 01, 2010 Nat Methods. 2010 Aug;7(8):634-6. doi: 10.1038/nmeth.1481. Epub 2010 Jul 18.
High-throughput in vivo vertebrate screening.
Zebrafish High-Throughput Screening of Innate Immune Responses.
Zebrafish Disease Modeling III, June 21-24, 2010 Dana-Farber Cancer Institute, Boston, MA
Herman Spaink¹, Ron Dirks², Jan de Sonneville¹, Ralph Carvalho², Oliver Stockhammer¹,², Ewa Snaar-Jagalska¹, Annemarie Meijer¹
June 21, 2010
Zebrafish High-Throughput Screening of Innate Immune Responses.
1Leiden University, Leiden The Netherlands; 2ZF-screens B.V. Leiden, The Netherlands
Zebrafish are an excellent model for studying the mechanisms of the innate immune defense against pathogens. A high throughput approach is described for a study of the innate immunity in response to bacterial pathogens. The COPAS flow cytometer provided the data analysis in a quick, unbiased and high throughput manner.
A High-Throughput Assay To Measure Whole Body Metabolic Rate Using Zebrafish Larvae.
2009 Lab Automation, January 25-28, Palm Springs, CA
Khadijah Makky1, Petar Duvnjak1, Kallal Pramanik2, Ramani Ramchandran2, and Alan N. Mayer1
January 25, 2009
A High-Throughput Assay To Measure Whole Body Metabolic Rate Using Zebrafish Larvae.
Department of Pediatrics, Gastroenterology1 and Developmental Biology Sections2, Medical College of Wisconsin and Children’s Research Institute, Milwaukee, WI 53226
Whole animal acid secretion can be used as readout for energy metabolism, thus enabling high-throughput chemical and genetic screens for regulators of metabolic rate in a vertebrate. The COPAS sorter was critical for automation.
A Whole-Animal Microplate Assay for Metabolic Rate Using Zebrafish
Makky K, Duvnjak P, Pramanik K, Ramchandran R, Mayer AN
November 18, 2008
Journal of Biomolecular Screening, Vol. 13, No. 10, 960-967 (2008)
DOI: 10.1177/1087057108326080
A Whole-Animal Microplate Assay for Metabolic Rate Using Zebrafish
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
To study genetics and drugs that impact metabolic rates, whole-animal acid secretion was used as an indicator for energy metabolism. Because of rapid kinetics, COPAS was used for large-scale screening of zebrafish.
Multiparametric analysis of neuromast hair cells in intact early larvae using a large particle sorter.
2005 West Coast Zebrafish Meeting, September 9 – 10
Bo Wang, Julia Thompson and Rock Pulak
September 09, 2005
Multiparametric analysis of neuromast hair cells in intact early larvae using a large particle sorter.
Union Biometrica Inc., 84 October Hill Rd, Holliston, MA 01746 USA
Drug Discovery - Automated Drug Screening Using Zebrafish: COPAS XL Allows for Increased Throughput
September 01, 2002 Genetic Engineering News Volume 22, Number 15, September 1, 2002, pp. 32, 35.