WP1: Excellence in ERIC operations and management

This ERIC central office lead WP lies at the core of our goal to improving the performance of the EU-OS RI. Uniform and transparent access procedures, based on the European Charter for Access to RI’s, for users from academia and industry will be implemented (in collaboration with WPs 2-5). The access procedures will be integrated into the CORBEL and EMBRIC project service pipelines. Informed by WP4 and WP5, within WP1 workshops will create workflows, handbooks and guides for new services in fragment-based screening/evolution, and chemical proteomics. To support the extension of membership, WP1 will organise national meetings to disseminate activities and strengthen national networks through lobbying of national funders and policy makers.

We will establish a global RI network in chemical biology through defined collaborations with excellent compound screening and medicinal chemistry platforms. A Partner Site Forum will be established and further evaluation rounds for partner sites from newly joined or prospective countries organized. In response to user and stakeholder feedback, we will refine and monitor our key performance indicators including gender-specific KPIs. These can include the monitoring of both genders in the management, dissemination and administration of the ERIC, including the participation in the WP leaderships and the distribution of tasks. An outcome of EU-OS-DRIVE, which takes into account all of the activities described above, will be a new business plan covering the period 2022 onwards, which will address financial and operational sustainability.

WP2: Academic compound acquisition

The European Academic Compound Library (EACL) is hosted at the Central Compound Management Facility of EU-OPENSCREEN ERIC in Berlin and foresees the integration of 40,000 compounds from academic chemists whose submitted compounds are exposed to user screens and biological targets. This process will catalyse cooperation between chemists and biologists facilitated by the expertise and technology of the screening centre, within an IP sharing model that rewards all parties.

In this WP, we will accelerate the acquisition process by establishing a network of scientists in ERIC member countries, “EU-OS Ambassadors”, who will solicit compound submissions from their national scientific communities and drive the crowd sourcing process through local contacts and building trust with submitting chemists. Workflows to identify, track and store these compounds were developed according to FAIR principles.

WP3: Demonstration of EU-OPENSCREEN’s integrated screening and medicinal chemistry capacities

We will use the instrument of transnational access to test the complete pipeline of EU-OS services, assessing both the performance of partner site and management workflows for compound screening, data handling and chemical optimization of hit compounds. This will build user trust with the ERIC not only among the user community but also with the partner site personnel. We will offer three different access tracks, covering biochemical/biophysical, classical cell-based and complex cellular assays. Access will be open to users from all European countries and up to two projects will be open for users from outside the EU.

The call for project proposals will draw attention of users to gender aspects in their research projects. Generated project data will assist in testing the European Chemical Biology database (ECBD) functionality with WP6. Expert scientists at the partner sites will dedicate time for practical training of users on the technology platforms.

WP4: Extension of capacities 1: fragment-based screening

Fragments are compounds with relatively low molecular weights and target affinities, which can bind important sites on proteins (eg catalytic or ligand domains) not accessible to screening compounds. In this WP, we will work directly with the INSTRUCT ERIC and the iNext consortium, which provide services in protein expression and purification, biophysical characterization and protein structure determination by X-ray and NMR. We will establish a fragment screening library of 1,000 highly-soluble compounds, perform quality control on the compounds, and provide logistics services at the compound collection management facility of EU-OPENSCREEN ERIC (CCMF).

Users will be able to screen the EU-OS fragment collection at INSTRUCT sites using X-ray, NMR and Cryo-EM based readouts. Procedures for data upload from the partner site into the ECBD database, tracking of biological results and data analysis tools will be implemented. An important aspect in this WP are consultancy services and workflows for users to perform chemical evolution on their hits. This new EU-OS capacity will add enormous value to structure based drug design projects for users globally, and eliminate a substantial bottleneck in this field.

WP5: Extension of capacities 2: chemical proteomics services

Currently, EU-OS partners provide access to phenotypic screening methods using high content and cellular readouts to identify hit compounds in disease relevant in-vitro models, where the underlying target or disease relevant pathway is unknown. The knowledge of a lead compound’s efficacy target is crucial for structure-activity-relationship (SAR) studies in medicinal chemistry programs, i.e. for the design of more potent derivatives of the compound based on its structural modification. Even if the efficacy target is known, many drugs show side- or off-target effects due to additional interactions with proteins that are not involved in the desired effect.

Thus, identifying drug-target interactions will dramatically help in optimizing a compound and predicting unwanted and potentially dangerous effects of the drug. Target identification services are not yet available within EU-OS, therefore in WP5 we will establish this as a new service using the instrument of transnational access calls for 6 suitable projects. Access will be open to users from all European countries and up to one project will be open for users from outside the EU. The call for project proposals will draw attention of users to gender aspects in their research projects. Chemistry partner sites in collaboration with partners with proven track-records in probe development, target deconvolution and mass spectrometry imaging, will perform this work.

Partner sites will profit from know-how transfer which will, in turn, ensure that the build-up of these capabilities will have a long-lasting benefit for EU-OS users. Linking the activities of this WP to other relevant RIs such as Euro-BioImaging or ELIXIR will generally support successful progression of chemical proteomics studies. Based on the experience gained, a handbook will be created in conjunction with WP1, which details access requirements and workflows for chemoproteomics services at EU-OS.

WP6: Improving data utilisation and impact for users

The ECBD will be implemented, as a publicly accessible database under ERIC funding, to hold screening, chemical and bioprofiling results, assay protocols and attendant metadata. In EU-OS-DRIVE WP6, our efforts will be directed to improving data workflows and transfers from screening and chemistry partner sites to the ECBD. Emphasis will also be put on the implementation of industry standards for data reporting such as the ‘Minimum Information About a Bioactive Entity’ (MIABE) and monitoring of compliance to these standards by our partner sites. Training in informatics tools to aid the analysis and selection of hit lists and identification of tool compounds will be delivered through workshops and tutorials in collaboration with WP8. The Institute of Molecular Genetics of the ASCR, v. v. i. (IMG) in the Czech Republic, the host of the ECBD under the leadership of Petr Bartunek, will lead this work package. This WP will also link into a demonstrator project in the European Open Screening Cloud (EOSC) Life project which plans to cloudify data sets from the ECBD and make them available as data resources to the wider community.

WP7: Industry engagement

An Industry Liaison Office (ILO), composed of members from the pharmaceutical industry, technology vendors and compound providers will be set up. The ILO supports EU-OS by attracting more SMEs to our compound library and screening capabilities. In parallel, we will provide short-term technology courses for industry scientists at our partner sites with WP8. We will proactively seek contacts with the pharmaceutical, agri-science, nutrition and biotechnology industries and give feedback on access and IP requirements when working with EU-OS. We will also improve the regional bioscience landscape, organising workshops and courses together with local industry partners.

Co-developments of novel screening technologies between industrial technology providers and specialized screening partner sites will be established. Exemplar topics for co-development with industry partners are implementation of routine and robust 3D screening systems and development of affordable high throughput label-free mass spectroscopy. The goal is to go complement EUOS’s core role as service-provider and build open innovation partnerships with industry, focused on codevelopment of novel enabling technologies.

WP8: Training

To promote convergence in technical capacities, we will set up staff exchanges for scientists coming from prospective partner sites in member and non-member countries. Users will receive practical training on assay development, automated screening, lead optimisation and data analysis. Quality training will empower users to establish new best practice at their own facilities. On-site training will be supplemented with webinars, and e-courses accessible via the EU-OS website and posted on YouTube and similar platforms.

Specialized training courses on fragment screening and target identification will be offered so new capabilities of the RI are transferred from expert to emerging sites and then on to external users (with WP4 and 5). A specialised course on advanced data mining and machine learning will be organized in connection with WP6. Advanced training of ERIC managers is an important measure to ensure scientific and financial sustainability. EU-OS leaders will continue their current RITRAIN management training, and 1-2 more managers will attend the course in the next years. Where it could benefit users, staff exchange between EU-OS and other ERICs will be supported. Training courses will be published on the EURAXESS portal.

WP9: Project management

The EU-OS Central Office will manage EU-OS-DRIVE reporting to the EU and contract negotiations with beneficiaries and third parties. In collaboration with WP leaders, it will manage the overall work plan, deliverables and milestones, including updates, changes or extensions of the work plan, The WP will also organise regular project meetings and teleconferences, prepare meeting minutes and support the set-up of, and communication with, the scientific and industry advisory committees. It will manage the communication related to the enlargement of EU-OS membership and is responsible for the main public relation activities.

Importantly, it will keep updates of all committed and spent resources and will track other project costs. To attract additional ERIC members we will collaborate with national chemical biology networks in countries which are not yet part of EU-OPENSCREEN. Reciprocal collaboration agreements with global screening and chemical biology organizations in countries such as Australia, India, South Korea, China and Canada will be set up, leading to sharing of compound, technology, and data resources for the benefit of all initiatives.

WP10: Ethics