Transnational Call - SMALL MOLECULE SCREENING
Under this call 12 EU-OPENSCREEN-DRIVE partner institutions will each offer one predefined screening technology to external users. The user will provide the biological question and the related assay matching the offered techniques. The offered screening technologies have been selected carefully to demonstrate the broad variety of screening capacities and expertise that can be provided by the EU-OPENSCREEN network. Read more about EU-OPENSCREEN here. Moreover, the technologies offered are divided into three access tracks representing increasing levels of biological complexity ranging from individual isolated proteins all the way to organoids and engineered micro tissues. Applicants from institutions within European Member States and Associated countries and up to 2 users from a Non-EU country are invited to review the offered screening technologies and apply to the one most suitable to their individual assay setup and biological question. EU-OPENSCREEN will provide its 100,000 compound collection for each of the 12 selected user projects. Read more about the EU-OPENSCREEN compound library here.
The successful applicant needs to provide an established biological assay running at lab-scale as well as key bespoke reagents. The small molecule screening projects comprise the following steps:
- Transfer of the assay provided by the user to the screening site
- Miniaturization of the assay into 384-well or 1536-well plate format
- Pilot screen using the 5,000 compounds EU-OPENSCREEN pilot library
- Analysis of pilot screen data
- Full screen with the remaining 95,000 compounds of the EU-OPENSCREEN compound library
- Data analysis and subsequent selection of primary hits
- Hit picking of primary hits for hit validation
- Hit validation (i.e., dose response curve and IC50 (or comparable parameter)-determinations)
- List with the "validated" hits will be provided to the applicant
Successful screening projects can subsequently apply for the medicinal chemistry call opening in the year 2021 for the chemical optimization of validated hits. Read more about the Medicinal Chemistry Call under the dedicated call.
The call for proposals will be open until September 30, 2019, 20:00 CET. Eligible proposals will be evaluated for scientific excellence, impact and technical feasibility. Proposals will be handled confidentially. Read more about the proposal submission, eligibility criteria, modality of access and evaluation processes below.
Track 1: Biochemical/biophysical assays
This track will address the needs of users with soluble protein targets seeking biochemical or biophysical assay readouts to identify modulators of enzymatic activity, protein-protein interactions, ligand binding to soluble receptors, etc.
The target class coverage offered is comprehensive, including, but not limited to kinases, phosphatases, proteases, transferases, gyrases, de-ubiquitinating enzymes, esterases, nuclear hormone receptors etc.
Successful applicants will be expected to have mature, tractable, pharmacologically relevant ‘benchtop’ assays in place in at least 96-well format, which can be adapted to automated screening conditions. Users must be able to provide essential access to well-characterized target-specific soluble reagents including enzymes, antibodies, etc., having suitable purity and activity to support assay adaptation to automated screening, primary screening and follow up studies.
Please see below our offers under this track:
Fraunhofer IME ScreeningPort (IME)
Enzymatic, binding or macromolecular interaction assays with stable optical readout
Institute of Molecular Genetics of the ASCR, vvi (IMG)
Screening for enzyme inhibition and protein binding
University of Bergen (UiB)
Screen for ligand-binding by differential scanning fluorimetry (DSF) using purified proteins as targets
Track 2: Cell-based assays using cellular systems
In this track, access to high throughput screening (HTS) services involving cellular systems will be provided. Cellular assays allow the robust identification of compounds that cause the desired phenotype and, in the case of intracellular targets, select for compounds able to cross the cell membrane and reach their site of action inside the cell. Suitable assays could allow the prediction of the response of a compound on an organism or disease model, whilst not having the handling, supply and complex culturing conditions associated with more complex cellular systems such as primary cells or iPS derived cell lines (covered in Track 3). Cell-based HTS services available to the user include, but are not limited to, the study of cell viability and proliferation, reporter protein activation, ion channel or GPCR modulation, intracellular signalling and disease relevant pathway analysis, cell migration and translocation, adhesion of cells to substrates or cell layers, etc.
Moreover, cell-based assays also allow modulation of targets not tractable in biochemical assays of Track 1 (e.g., enzyme complexes involving multiple components and co-factors).
Users must be able to provide access to target or model specific cell lines and associated bespoke reagents (e.g., target or pathway specific antibodies), which would support assay adaptation to automated screening, primary screening and follow up studies.
Please see below our offers under this track:
Helmholtz Centre for Infection Research (HZI)
Screening for novel anti-infectives targeting either the pathogen (up to BSL-3) or the host
Institute of Molecular and Translational Medicine, Palacky University (IMTM)
Phenotypic or targeted cellular screen based on high-content analysis
Fundación MEDINA (MEDI)
Real-time kinetic cell-based assays using the FLIPR Tetra HTS system
University of Helsinki (UH)
Cell-based screen using an established cell line
University of Santiago de Compostela (USC)
Screening of biased and allosteric compounds at G protein coupled receptors (GPCRs) by multiplexing different signaling pathways
Track 3: Cell-based assays using complex cellular systems
Complex cellular systems including those based on human iPS lines, primary human cells or other non-human complex cellular models (e.g., plant cells) enhance the physiological relevance of the obtained assay results, albeit there are typically significant complexities associated with reagent generation and assay design. Nevertheless, primary patient derived and iPS lines, for example, are superior to established cell lines in mimicking processes in health and disease and do not bear some cell line specific artefacts (e.g., passage related loss of genetic information). Offering iPS cell-based assays will also allow the user to run chemical screens on cell types otherwise not available in significant quantities (e.g., neuronal or cardiac cell types). In addition, the use of complex systems including organoids and micro tissues will enable the user to study cell-to-cell communication in a 3D-like context more closely resembling the in vivo situation.
Please see below our offers under this track:
Príncipe Felipe Research Center (CIPF)
Complex cellular-HTS based assays for modulation of tumor microenvironment and metastasis.
Leibniz Research Institute for Molecular Pharmacologie in the Forschungsverbund Berlin e.V. (FVB-FMP)
2D imaging of cellular systems (spheroids, organoids from iPS or primary cells) to identify compounds interfering with cancer development or other signaling pathways.
Institute of Bioorganic Chemistry, Polish Academy of Sciences (IBCH-PAS)
High capacity and combinatorial screening to find biologically-active molecules and optimize their mixtures for maximal efficiency and synergy identification (e.g. on human and plant cell lines, as well as iPS)
Centre for Molecular Medicine Norway, University of Oslo (UiO-NCMM)
Screening project assessing characteristics of suspension cells using flow cytometry.
