Infrastructure for transnational access and discovery in structural biology

Informations projet

iNEXT-Discovery

N° de convention de subvention: 871037

DOI

10.3030/871037

Projet clôturé

Date de signature de la CE 16 Decembre 2019

Date de début 1 Février 2020

Date de fin 31 Juillet 2024

Financé au titre de

• EXCELLENT SCIENCE - Research Infrastructures

Coût total

€ 9 987 743,83

Contribution de l’UE

€ 9 987 743,83

Coordonné par

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Netherlands

Periodic Reporting for period 3 - iNEXT-Discovery (Infrastructure for transnational access and discovery in structural biology)

Période du rapport: 2023-02-01 au 2024-07-31

Résumé du contexte et des objectifs généraux du projet

For four-and-a-half years, iNEXT-Discovery, the "infrastructure for translational access and discovery in structural biology", was able to increase the impact of structural biology for innovative biomedical, biotechnology, food science, and biomaterials research. The consortium of thirty leading academic groups shared their expertise, equipment and facilities for state-of-the-art X-ray techniques, ultra-high field NMR, modern cryo-EM, and other biophysical techniques. A large networking program informed large scientific and other communities of the advantages of structural biology, and together the partners in the project developed the new tools, methods and protocols to apply their methods faster and better.

The main objective of the project was to prepare and provide free-of-costs transnational access services for external researchers, either through physical visits or remotely. To address and achieve many priorities, the efficient streamlining of all activities has been key, always keeping an outlook towards long-term sustainability and efficient data management. Partners were meeting frequently, also reaching out to external scientists from many different academic communities. We heavily invested to reach the general public, the private sector and 'regional structural biology communities'. The theoretical and practical training of (young) researcher has been a major focal point, and our internal joint research activities delivered many tools to improve methods and the quality of facility access.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Next to serving a loyal community of technology experts, a particular challenge was to provide structural biology access to non-experts. The highly skilled facility staff operating the 25 research facilities that contributed to iNEXT-Discovery, has been instrumental for safeguarding many different user projects.

The iNEXT-Discovery website, hosted by Instruct-ERIC, featured a continuous portal for user proposal submission that allowed access requests to our versatile methods catalogue. To specifically highlight specific topics or to address certain research communities, calls-for-proposals were initiated, including some with other research programs. When suitable, the output from the consortium's joint research has been implemented and rolled out to access providers, to improve and harmonize existing and new structural biology methodology and applications.

At the end of the project, external reviewers processed over 670 user proposals containing 720 different access requests. We were able to provide experiments for 525 user submissions, either with users visiting the facility or remotely, thereby serving over 500 different researchers. After the corona-pandemic, in-person visits to facilities flourished again, typically allowing hands-on training of early-career scientists by expert staff. Overall, our access operation has been very successful and well-appreciated by the European user community and beyond.

The second half of the project allowed us to catch up with our pandemic-delayed program of practical workshops and other in-person events, and we assured our in-person visibility through discussions, posters and presentations at many scientific meetings. The online training material we prepared earlier in the project has been linked to our website, and this website will remain operational also after iNEXT-Discovery to illustrate the objectives, methodologies and other useful information about structural biology approaches also in the future.

A wide variety of activities, in part supported by the ESFRI Research Infrastructures involved, informed a steadily increasing population of all benefits of structural biology for biological, biomedical, biotechnological, food and other life sciences, and attracted researchers to our events and services. We have been operating on many regional, national and international platforms to showcase the use of high-end structural biology methodology and applications, and mobilized academia and other communities to interact with us and with each other.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Also by embracing exciting new achievements in cryo-EM and AI-driven structure predictions, iNEXT-Discovery brought innovative structural biology approaches to a growing life science community. Several of our activities led to exciting new methodological advances:

1. Fragment-based drug discovery, where hundreds of small chemicals are tested for binding “targets” is increasingly used, also by pharma and biotech, to pick up compounds that interfere with biological function. FBDD has been a flagship access service in the project, and for maximizing output we developed tools that allow streamlining and evaluation of an enormous amount of experimental screening data in real-time. Moreover, as the focus of FBDD has been somehow restricted to find successfully binding compounds, we invested with PDBe (the well-known Protein Data Bank in Europe) in an open data repository for storing and managing complete fragment screening campaigns.

2. By delivering new tools and data handling, iNEXT-Discovery has been key for increasing throughput of data acquisition and analysis for cryo-EM. Cryo-EM grid preparation and screening of grid ice thickness are now largely automated, as well as cryo-EM and tomography sample evaluation and data pre-processing.

3. iNEXT-Discovery provided new approaches that simplify the study of biomolecular conformations and their behavior on different time scales, also in living cells. We advanced time-resolved NMR and created tools for studying RNA and light-sensitive systems. We tested novel protocols for kinetic ssNMR to study drug-receptor interactions, and developed prototype equipment and workflows for using in-cell NMR bioreactors, also to offer user access to these in our facilities.

4. To assist cellular imaging by structural biology, a strongly upcoming field, we improved Focused Ion Beam milling for cryo-EM and soft X-ray tomography automation, and we managed to correlate these with super-resolution fluorescence microscopy. Tools were prepared to better combine X-ray scattering with solution NMR to study flexible macromolecules, whereas new solid-state NMR procedures allow now studies of protein dynamics and integration with cryo-EM analyses.

The scientific impact of the iNEXT-Discovery project is indisputable, and not only from the 233 Open Access publications that report on new methodology and user applications. This is already more than 50 publications per iNEXT-Discovery year (!), and we know that this output will grow further after the end of the project. Many of our achievements will be available also for future facility access, since the developed tools, pipelines and approaches will be rolled out to other facilities, in many cases hosted by Instruct-ERIC. Long-term impact has also been achieved through providing theoretical and on-site practical training in modern structural biology methods and their applications. Both these and our joint research program were very helpful to wider educate the life scientists that are needed in academia and industry for modern translational research.

The tangible success of iNEXT-Discovery, serving many hundreds different researchers in Europe, its widening countries and beyond, highlights once more that structural biology research will also remain a future socio-economic stronghold, essential for efficiently tackling societal challenges for health, food and biotechnology.

iNEXT-Discovery Summary