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The Screening Unit provides an open access high throughput technology platform for screening compound libraries (170.000 drug like compounds) and for genome-wide RNA-interference or CRISPR-Cas9 gene-editing (human and mouse) using automated microscopes and a broad panel of other devices (see >Technologies).
High-throughput testing of compounds and identification and validation of novel targets
The Screening Unit serves as an open-access technology platform for automated screening, using either compound libraries (~170,000 compounds) or genome-wide RNAi libraries (human, mouse, nematodes). The platform is typically a part of scientific collaborations, and its primary aim is to make possible the use of drugs in academic research for analysis of molecular mechanisms in disease and development. Besides supporting assay development, process automation, screening and automated data analysis, the Unit engages in the identification of novel screening technologies. The Unit supports screening projects in assay development and optimization of high-throughput compound screening (HTS, Silke Radetzki), as well as automated data documentation and analysis (Martin Neuenschwander). Genome-wide RNAi and CRISPR-CAS screening (HTS, Katina Lazarow) has been added for the identification and validation of novel cellular targets in disease. In 2019, we started applying 3D analysis with a confocal microscope and morphological pattern analysis to profile drug effects in cell culture systems (Christopher Wolff). The Unit is building a central core facility for drug screening on the Campus Berlin-Buch for the Helmholtz Drug Research Initiative and for EU-OPENSCREEN.
Pictures demonstrate translocation of beta-Catenin (red) to nucleus (yellow) as a result of mutations in origin of many human tumors (picture left), live cell imaging of protein kinase C (yellow) after modulation of an ion channel (central picture), a cell culture model for metastasis of human tumor cells (actin staining red and nuclear staining green, picture right).
Project Application
You may contact us via E-Mail, see Contact.
For effective support and data documentation you need to fill in the requested information and send us the project application form
Project application form for screening the FMP library
Project application form for screening the EU-OS library
Assay Setup
You may visit the Screening Unit, where we can help you in assay transfer to the 384well format and test your assay set up together for HTS usage. You will then be able to update the project application form with the revised protocol. Afterwards the materials for your next visit and primary screen plus validation are calculated.
Primary Screen
We perform the primary screen together with one person from your team, the data are documented and analyzed automatically. You receive the raw data, statistic analysis, and statistics-based hit lists containing also structural data.
Review of hit lists
If desired, you may revise the hit lists. You send us a list of 352 compounds via e-mail.
Cherry picking
We provide you with a 384-well plate containing your requested 352 hits, (4 µl 5mM compound in DMSO).
Quality control of 352 hit compounds via LC-MS Analysis
A small aliquot (0.2 µl) of your hit picking plate is taken and diluted in ACN/H2O for the LC-MS analysis. We analyze the samples in ACN/H2O (1:1, 25 µM) with our Agilent TOF mass spectrometer and determine the purity via UV absorption at 254 nm.
IC50 validation
IC50 validation (using nine serial dilutions of the compounds in duplicate) is carried out by us, the data are analyzed automatically. You receive for a maximum of 352 "hit" compounds IC50 reports containing MS analysis data, frequent hitter information, data from biophysical and cytotox profiling. To our experience less then 10% of the compounds from the hit list of 352 can be expected to be true hits.
Review of IC50 data
Our chemists revise with you the list of validated compounds and suggest proposals, which compounds might be selected for further characterization and optimization of leads.
Please bear in mind that all steps need only to be performed once per project!
The Screening Unit can assist your project with know-how gained from about 170 previous screens. But the data documentation, analysis and follow up studies are in the responsibility of the PI of the project.
The facility offers scientists from the FMP and MDC access to high-throughput screening with arrayed miRNA, siRNA and sgRNA libraries on the basis of a scientific collaboration.
Broad range of assays
State of the art equipment supports a broad range of assays in high-throughput formats, ranging from basic reporter assays to high-content screening campaigns. Instrumentation covers automated fluorescence microscopy, flow cytometry, luminescence and real-time kinetic fluorescence reading (see Technologies).
Full support in high-throughput screening
We operate on the basis of a scientific collaboration and offer support through all stages of a screening campaign: assay development and adaption to high-throughput screening, the actual wet-lab screen, data acquisition and quality assessment, statistical analysis as well as hit candidate selection.
Data processing
We are constantly advancing our in-house analysis, database and reporting tools to keep the platform updated. The integration of freely available open-source tools (e.g. KNIME Analytics Platform) and the development of our own analysis workflows enables us to meet the specific requirements of a multitude of biological questions.
Ermanno Gherardi, MRC Cambridge (UK), 2008
Michael Salcius, Yale University, 2009
H. Funke-Kaiser (Charité, Berlin), 2010
People
Head of Screening Unit
Process Automation and HTS Data Analysis
RNAi and CRISPR-based Screening
Cell Biology and High Content Screening
Core Facility siRNA Screening
The Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) is part of the Forschungsverbund Berlin e.V. (FVB), which legally represents seven non-university research institutes - members of the Leibniz Association - in Berlin.
Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10,
13125 Berlin, Germany
