University Medical Center Utrecht
Heidelberglaan 100 Room H02.313 3584 CX Utrecht The Netherlands
Dr. D.A. Egan
+31 (0) 88 756 8219
The Cell Screening Core, (CSC), is a well-established center for high throughput screening. The Core is a center of excellence for High Content Screening, (HCS). This powerful technology combines the automation of cell-based morphological assays with automated microscopy, automated image analysis, and advanced data mining techniques. It increases the scientists chances of finding interesting, relevant hits from screens and can give an early insight into mechanism of action. We have developed a proprietary software tool for the mining of HCS datasets called HC StratoMineR. The addition of this software platform has established the CSC as the only academic center in the Netherlands that can offer a complete fully automated HCS service.
We run screens for wide variety of applications drug target discovery, and chemical biology/drug discovery. The CSC can screen libraries of chemicals, siRNAs, miRNAs and other reagents. The center has the required laboratory facilities, robotics, bioinformatics infrastructure and expertise to successfully run fully automated high throughput chemical biology and functional genomics screens in 96- or 384-well plates. As well as HCS we can also run traditional HTS projects. We routinely run assays using 2D cell culture models but 3D models can also be run. In collaboration with the Bos & Clevers groups at the UMCU & Hubrecht Institute we have developed technologies for the automation of cancer organoid screening.
The Center offers a highly personalized, collaborative service in which we work closely with our clients to help them to achieve their goals, with high levels of quality and affordable costs. The CSC was established by Dr. David Egan who has extensive experience in automated screening in academia and the pharmaceuticals industry. The CSC can therefore offer clients access to a combination of industrial experience with the support of academic knowledge and innovation.
The CSC is located on the campus of the University Medical Center Utrecht and is embedded within the UMCU Department of Cell Biology. The department has an excellent international reputation in the field of cell biology and is an integrated academic center for fundamental and translational research.
The Center operates on a ‘technology hotel’ model. Assay development and validation is carried out by the project team in consultation with the CSC. The CSC then develops and validates protocols so that assays can be run in an automated fashion. The screen is run on the CSC robotics platform by the project team, with the appropriate level of oversight and assistance from CSC staff. The Center is open to academic research groups from throughout the Netherlands.
- Biomedical & health
- High throughput screening
- High content screening
- Assay development and miniaturization
- Organoid screening
- Advanced data mining
- Stem Cell Biology
- Chemical Biology
Expertise and Track Record
435000010 High content analysis for the characterisation of novel disruptors of GHR-JAK2 signalling with prof.dr. J. Klumperman (UMC Utrecht)
At the Dutch level we are the most advanced academic facility for fully automated high content screening services. At an international level we would be comparable with leading facilities.
Multiple Myeloma – Anton Martens
We have used our Prestwick Chemical Library of 1200 drugs to screen for drugs that specifically kill multiple myeloma cells in a co-culture system. We used a luminescence based readout for myeloma cell viability and the assay was carried out in 384-well plates.
Chromatin Modification – Marc Timmers
We have used a library of siRNAs that target chromatin modification genes in combination with fully automated immunocytochemistry in multiple cell lines to screen for genes that affect the extent of a number of DNA and histone modifications. This allows us to build a profile of chromatin modification phenotypes for genes and to determine the differences in the profiles in multiple cell lines. Cells in all cases are imaged using automated microscopy and automated image analysis.
Mitotic Spindle – Rene Medema
A genome-wide siRNA screen was carried out to identify genes involved in spindle formation in mitosis. The readout was based on fully automated immunocytochemistry in 384-well plates. The cells were imaged using automated microscopy.
Proteomics & Functional Genomics – Madelon Maurice
Madelon Maurice at the UMCU has performed elegant experiments with proteomics approaches to identify novel members of the Wnt receptor complex. The data from these studies guided the generation of a custom siRNA library at the CSC that was used to functionally validate their involvement in Wnt signaling.
- In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells. Prins HJ, Braat AK, Gawlitta D, Dhert WJ, Egan DA, Tijssen-Slump E, Yuan H, Coffer PJ, Rozemuller H, Martens AC. Stem Cell Res. 2013 Dec 12;12(2):428-440.
- A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels. Baas R, Lelieveld D, van Teeffelen H, Lijnzaad P, Castelijns B, van Schaik FM, Vermeulen M, Egan DA, Timmers HT, de Graaf P. J Biomol Screen. 2014 Feb;19(2):287-96.
- High-content screening of peptide-based non-viral gene delivery systems. de Raad M, Teunissen EA, Lelieveld D, Egan DA, Mastrobattista E. J Control Release.158:3 433-42, 2011.
As part of the UMCU Department of Cell Biology we are involved with the NL BioImaging initiative. Our role in this consortium is as a center of excellence in automated microscopy and high content screening.
- 1 dedicated postdoc
- 1 dedicated technician
- 1 lab manager
- Caliper Sciclone - Robotic Liquid Handling; Thermo ArrayScan - Automated Microscope; Thermo CellInsight - Automated Microscope; Thermo MultiDrop Combi - Bulk Dispenser; Tecan HPD300 - Picoliter Dispenser
Yes, Cellomics Store High Content Database