Screening Unit

Introduction

Four 384tip pipetting systems enable one to test up to 160.000 compounds per day for their biological effects. (foto: Lothar-Michael PETER, www.foto-LMP.de, info@foto-LMP.de)
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Cytotoxic potential of compounds identified by fluorescent staining of cellular structures. Light blue nuclei mark cells with damaged membranes, while red fluorescence marks functional mitochondria.

The FMP hosts the central open access technology platform of EU-OPENSCREEN, the ChemBioNet, the Berlin Institute of Health, and theHelmholtz-Initiative für Wirkstoffforschung, the Screening Unit. The Unit serves for systematic screening of large compound or genome-wide RNAi libraries with state-of-the-art equipment like automated microscopes and microfluidic systems (see also "Technologies") within EU, BMBF, DFG and regionally funded academic networks.

The mission of the platform is to enable access for academic projects towards experiments in high-throughput without loss of IP and on a cost basis, which does not restrict access towards HTS usage.

The Screening Unit is part of the Chemical Biology Platform of the FMP also supported by the MDC. This platform extends collaborative support through the Screening Unit (Jens Peter von Kries) by Medicinal Chemistry (Marc Nazaré) and by Drug Design (Ronald Kuehne).

Within this platform the mission of the Screening Unit is to

  • provide well designed (World Drug Index derived druglike scaffolds) screening collections (60.000 cpds) including 1018 FDA approved drugs (SELLECK library), 1280 compounds with annotated activities (LOPAC library) and novel molecules synthesized and donated from academia (about 4.000 cpds). 20.000 cpds are either natural product derived synthetic molecules or purified from plants or bacteria provided by (Analyticon Discovery GmbH). For a detailed overview please follow this link.
  • provide additional hundred thousands compounds from EU-OPENSCREEN
  • identify bioactive small molecules as tools for modulation of biological functions for research termed Chemical Biology.
  • downscale test volumes ( low volume 384well plates: minimum 5 µl) to reduce costs for expensive reagents

More then 250 screening projects (Highlights) have been already supported in EU (MolDiaPaca, SFMET, AntiFlu), BMBF (Mtub, GoBio, NGFN...), DFG (FG-806) and TSB/IBB (Profit) funded work. Three projects are already either at the beginning or within clinical trials for patients suffering from cancer or rare disease like head stroke due to malformation of blood vessels.

The Unit served for academic and SME partners:

  • dnaAcos, Oslo (Norway)
  • Redoxis, Gothenburg (Sweden)
  • Jerini AG, Berlin (Germany).

For development of hardware:

  • Tecan Austria & Switzerland
  • Cellomics Inc. (Thermofisher)

Data documentation and analysis have been automated according to defined standard operating procedures and analysis pipelines. About 40.000 compounds can be screened (per pipetting workstation, total of 4) and analyzed in a single day (12 hrs) depending on the test system/detection method used. A complex set of reports containing heat maps, different statistical analysis routines, similarity clustering and inter screen analysis for identification of frequent hitters is provided.

Furthermore the Screening Unit tests novel detection systems, develops analysis and object identification routines, and in the case of positive outcomes integrates these into the daily screening service. For instance the usage of machine learning routines in collaboration with the ETH-Zürich for automated object identification in screening with automated microscopes. The latest technologies integrated are

  • label-free impedance measurement  (Excelligence, 96well/384well)
  • surface plasmon resonance             (Biacore T200)
  • high speed kinetic imaging               (FLIPR-Tetra)

(see "Technologies" for more detail).

Beside this service, the Screening Unit also manages the technology platform for genome-wide RNA-interference of the Max-Delbrueck-Centrum for Molecular Medicine (MDC) and the Berlin Institute for Medical Systems Biology to be used for Systems Biology in C. elegans, mouse and in human cell lines.

IMPORTANT NOTICE: As genome-wide RNA-interference may require large amounts of expensive liposome reagents to screen up to 800 MTP´s in 384well format, it is a very expensive approach, especially in combination with dual-luciferase reporters. Therefore you may wish to contact us to discuss alternative reporter systems and to estimate the required funding budgets.

 

  

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)
info(at)fmp-berlin.de