Transnational Call

SMALL MOLECULE SCREENING

 

Small molecule screening call

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:

  1. Transfer of the assay provided by the user to the screening site
  2. Miniaturization of the assay into 384-well or 1536-well plate format
  3. Pilot screen using the 5,000 compounds EU-OPENSCREEN pilot library
  4. Analysis of pilot screen data
  5. Full screen with the remaining 95,000 compounds of the EU-OPENSCREEN compound library
  6. Data analysis and subsequent selection of primary hits
  7. Hit picking of primary hits for hit validation
  8. Hit validation (i.e., dose response curve and IC50 (or comparable parameter)-determinations)
  9. 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.

 

Small molecule Call Overview / Basic Data

Topics / Keywords:

drug discovery, small molecules, high-throughput screening, biochemical/biophysical assays, cell-based assays

Open Time:

Start date:
June-01-2019 (20:00 CET)

Closing date:
September-30-2019 (20:00 CET)

Notification to applicants:
by mid December 2019 CET

Projects start date:
February-01-2020 (tentative date).
A delay in starting projects must be discussed with the partner institution of interest.

Contact: 

help-desk-open-call@eu-openscreen.eu

indicating "EU-OPENSCREEN-DRIVE Screening Call 1"

in the email subject

Application requirements and submission for all tracks / projects of this call

Proposal submission

  • Applicants are invited to submit their proposals via EU-OPENSCREEN-DRIVE website, by connecting to the ARIA online proposal submission system (online system will be available by June 1st 2019 (20:00 CET). Applicants are required to register upon their first visit to ARIA, or login directly if they are already registered with an ARIA account. Once registered, the applicants are required to follow ARIA instructions.
  • The online proposal submission will be open until September 30, 2019 (20:00 CET).
  • The ARIA application platform for EU-OPENSCREEN-DRIVE is handled by Instruct-ERIC. Although potential EU-OPENSCREEN-DRIVE users are requested to register with the ARIA system, the application, review, and reporting process will be handled by EU-OPENSCREEN ERIC staff members.  Applicants are invited to choose one out of the 3 tracks, which represent the core competencies of EU-OPENSCREEN-DRIVE screening partners, and apply to one of the screening technologies offered by the 12 individual institutions.
  • Applicants will be notified about acceptance or rejection of their proposal within 12 weeks after the closure of the small molecule screening call. If you have any doubt or question relating to the submission process within ARIA please contact us at aria@eu-openscreen.eu (indicating “EU-OPENSCREEN-DRIVE screening call” within the subject).

Eligibility criteria

  • Applicants may come from academia or industry (including SMEs).
  • Applicants may work in an institution of a European Member State or Associated State. Up to 2 projects will be open to applicants from outside Europe.
  • User access is transnational only. Users are not allowed to access facility(ies) in their home country. Please consider this when selecting one of the 12 offers. 
  • Principal investigators and members of their research groups from EU-OPENSCREEN-DRIVE beneficiaries are not eligible to apply.
  • Applicants commit to have legal and ethical consent regarding their research, their samples and/or their data
  • Applicants must agree to comply with EU-OPENSCREEN ERIC/EU-OPENSCREEN-DRIVE privacy policy and terms of submission.
  • Applicants must agree to comply with the access, IP and dissemination policies described in the statutes of EU-OPENSCREEN ERIC.
  • If you have any doubt or question relating to the eligibility criteria for this call please contact us at help-desk-open-call@eu-openscreen.eu (indicating “EU-OPENSCREEN-DRIVE screening call” within the subject).

 

 

Modality of access

  • Access will be free-of-charge for the successful applicants, working in an institution or industry of a European Union Member State or Associated country. Up to 2 projects can be allocated to applicants from outside Europe.
  • User access is transnational only. Users are not allowed to access facility(ies) in their home country.
  • EU-OPENSCREEN-DRIVE will ensure access to the EU-OPENSCREEN compound collection and logistics services provided by EU-OPENSCREEN Central Compound Management Facility (CCMF). Access is provided as an in-kind-contribution by the EU-OPENSCREEN ERIC. Read more about our compound collection here.
  • Applicants are invited to choose one out of the 3 tracks, which represent the core competencies of EU-OPENSCREEN-DRIVE screening partners, and apply to one of the screening technologies offered by the 12 individual institutions. Please note that, upon evaluation, proposals might be reallocated amongst the 12 participating screening institutions according to the research proposed by the applicant, the strengths of specific methodologies and expertise of the respective facilities. Herein, the transnational access rules imposed by the European Commission will be followed.
  • EU-OPENSCREEN-DRIVE will fund costs of successful projects for instrumentation time, consumables, regular assay readout reagents, shipment of delicate material and for personnel required at the facilities.
  • Users are also invited to apply for potential reimbursements of individual travel and accommodation expenses at the access facility directly in accordance with the facility´s rules for external user’s reimbursements. Each visit (if applicable) must be discussed and agreed with the EU-OSPENSCREEN-DRIVE management team (help-desk-open-call@eu-openscreen.eu) and access facility contact (please see email address under the partner site-dedicated section).
  • The applicant is expected to contribute bespoke reagents (e.g., specific antibodies for a target) and/or biological targets (e.g., protein of interest, cell lines or complex cell samples) for the screen. For more detailed information please contact the partners site of interest.
  • Project-related costs (personnel, consumables, and other costs) at the user laboratory are not funded under this call.
  • EU-OPENSCREEN-DRIVE recommends users to contact EU-OPENSCREEN-DRIVE team by email at help-desk-open-call@eu-openscreen.eu or the facilities offering the technology of interest in order to discuss the feasibility of the project prior the submission of the proposal (please indicate “EU-OPENSCREEN-DRIVE screening call” within the subject).

Proposal evaluation

The review process of applications consists of two steps of evaluation (1. scientific and 2. technical). The application will remain strictly confidential throughout the review process. Reviewers will be bound by a non-disclosure agreement.

  1. If eligibility criteria are met, 2 independent external experts in the field of small-molecule screening will evaluate the scientific excellence of the proposal. Societal impact and gender aspects of the project-specific research questions and method will also be considered.
  2. Technical feasibility will be assessed by internal EU-OPENSCREEN-DRIVE partners of interest and the EU-OPENSCREEN-DRIVE management support team. Herein, the degree of pharmacological validation of the user’s assay in a microplate format, suitability for transfer to automated screening and availability of key bespoke assay reagents will be of particular relevance. Moreover, technical reviewers will assess whether appropriate resources for the technical implementation of the projects are available at the partner sites.

 

 

Publication

Open access (gold or green) is required for any publication of access results. EU-OPENSCREEN-DRIVE funding must be clearly acknowledged by: “This project has received funding from the European Union´s Horizon 2020 research and innovation programme under grant agreement No 823893.”