Periodic Reporting for period 2 - iNEXT-Discovery (Infrastructure for transnational access and discovery in structural biology)
Okres sprawozdawczy: 2021-08-01 do 2023-01-31
iNEXT-Discovery, the "infrastructure for translational access and discovery in structural biology", aims to increase the impact of structural biology on innovative biomedical, biotechnology, food science, and biomaterials research. The consortium combines thirty well-known European academic structural biology groups that share their expertise and equipment for state-of-the-art X-ray techniques, ultra-high field NMR, modern cryo-electron microscopy, and molecular biophysics experiments.
Transnational access is made available to external researchers either through physical visits or remotely, the latter turned out an essential asset during the Covid-19 pandemic. Access is free of costs for facility users for research projects that are approved by peer-reviewers. Efficient streamlining of all activities with an outlook towards long-term sustainability and efficient data management are among many other priorities of the project. Underlying networking takes place between the partners and with external scientists from industry and academia, but also with the general public and with researchers from many life science communities. Theoretical and practical training remains a major focal point for our consortium, whereas our internal joint research delivers the tools that improve the throughput and quality of facility access services.
Transnational access is made available to external researchers either through physical visits or remotely, the latter turned out an essential asset during the Covid-19 pandemic. Access is free of costs for facility users for research projects that are approved by peer-reviewers. Efficient streamlining of all activities with an outlook towards long-term sustainability and efficient data management are among many other priorities of the project. Underlying networking takes place between the partners and with external scientists from industry and academia, but also with the general public and with researchers from many life science communities. Theoretical and practical training remains a major focal point for our consortium, whereas our internal joint research delivers the tools that improve the throughput and quality of facility access services.
One challenging objective of iNEXT-Discovery is provision of structural biology access to non-experts - especially to those willing to expand their methods portfolio - while at the same time our facilities also serve experts. As a result, facility staff can be involved at different stages of many user projects, with activities ranging from proposal preparation to data acquisition, data analysis and assisting the preparation of manuscripts for publication.
A single point of applications on the iNEXT-Discovery website allows the continuous submission of requests for access from our methods catalogue. In addition, to specifically highlight certain topics or research communities calls-for-proposals are being issued, also with other research programs.
Now, three years into the project, already over 400 user proposals have been received and processed. Of these, 230 received access, serving over 500 different scientists. Even after Corona-restrictions subdued a lot of access is given remotely, with facility operators performing the experiments for applicants. More recently, in-person user visits to facilities became possible again, which allowed again training of early-career scientists by expert staff. Overall, our access operation is well-appreciated and user feedback has been very positive throughout.
Through a wide variety of networking activities iNEXT-Discovery informed and attracted a steadily increasing number of biological, biomedical, biotechnological, food and other researchers. We are frequently participating on international platforms to showcase the benefits of high-end structural biology approaches and applications and mobilize academic and company scientists and communities to interact with us and with each other. At the same time, we work hard to stimulate interactions with funding agencies, policy makers and the general public.
Last year we caught up with our delayed program of practical workshops and other events, and we intensified our in-person presence at many scientific meetings. With our online training material, including new video footage, we provide “virtual tours” to illustrate our objectives, methodologies and other useful information about structural biology approaches.
Key to the success of the project, frequent discussions between iNEXT-Discovery management and external panels and Scientific Advisory Board take place, and their advices remain instrumental for the success of the project and for keeping our activities fully in-sync with ongoing developments.
Finally, our well-designed joint research program progresses extremely well, as iNEXT-Discovery partners collaborate to improve structural biology methodology and applications that rapidly become available also to other structural biology facilities and life science communities.
A single point of applications on the iNEXT-Discovery website allows the continuous submission of requests for access from our methods catalogue. In addition, to specifically highlight certain topics or research communities calls-for-proposals are being issued, also with other research programs.
Now, three years into the project, already over 400 user proposals have been received and processed. Of these, 230 received access, serving over 500 different scientists. Even after Corona-restrictions subdued a lot of access is given remotely, with facility operators performing the experiments for applicants. More recently, in-person user visits to facilities became possible again, which allowed again training of early-career scientists by expert staff. Overall, our access operation is well-appreciated and user feedback has been very positive throughout.
Through a wide variety of networking activities iNEXT-Discovery informed and attracted a steadily increasing number of biological, biomedical, biotechnological, food and other researchers. We are frequently participating on international platforms to showcase the benefits of high-end structural biology approaches and applications and mobilize academic and company scientists and communities to interact with us and with each other. At the same time, we work hard to stimulate interactions with funding agencies, policy makers and the general public.
Last year we caught up with our delayed program of practical workshops and other events, and we intensified our in-person presence at many scientific meetings. With our online training material, including new video footage, we provide “virtual tours” to illustrate our objectives, methodologies and other useful information about structural biology approaches.
Key to the success of the project, frequent discussions between iNEXT-Discovery management and external panels and Scientific Advisory Board take place, and their advices remain instrumental for the success of the project and for keeping our activities fully in-sync with ongoing developments.
Finally, our well-designed joint research program progresses extremely well, as iNEXT-Discovery partners collaborate to improve structural biology methodology and applications that rapidly become available also to other structural biology facilities and life science communities.
Through iNEXT-Discovery, unprecedented progress in innovative structural biology research has been realized, both through our extensive access program and through creating methodological advances from our joint research:
1. In Fragment-based drug discovery, hundreds of small chemicals are being added to “targets” to pick up compounds that interfere with function. FBDD is a flagship access service for our facility users, and for maximizing its output we developed novel software tools that allow the evaluation of an enormous amount of experimental data in real-time. Moreover, a new open data repository for storing complete fragment screening campaigns is being developed in a shared effort with PDBe, the well-known Protein Data Bank in Europe.
2. Another exciting focal point of our internal research program is to increase the throughput of data acquisition and analysis for upcoming structural biology technologies. Cryo-EM grid preparation and pre-screening of grid ice thickness are now largely automated, as well as cryo-EM and serial crystallographic sample evaluation and data pre-processing.
3. Besides static structures of biomolecules, also their behavior over different time scales and their multiple conformations and dynamics are crucial for understanding biological processes. In iNEXT-Discovery, new methods have been pursued that are being extensively tested and streamlined. The NMR-facilities involved advanced time-resolved NMR, and they generated tools for studying RNA and light-sensitive biomolecules. Emerging protocols also allow kinetic NMR on cell surfaces for studying drug-receptor interactions, and we provided prototype equipment and workflows for using bioreactors for in-cell NMR on living systems.
4. Cellular imaging by structural biology is a strongly upcoming field. For developing this, our partners streamlined Focused Ion Beam milling workflows for cryo-EM and soft X-ray tomography automation, and even managed to correlate these methods with super-resolution fluorescence microscopy. Moreover, tools were prepared that facilitate the straightforward combination of X-ray scattering and solution NMR data to study flexible macromolecules, whereas new solid-state NMR tools were created that allow the study of protein dynamics and can be integrated with cryo-EM analyses.
Overall, the scientific impact of iNEXT-Discovery is already evident from over 140 Open Access publications. These describe our technological structural biology advances and user-driven applications for life sciences, drug development, and so forth, and we know that our output will continue to grow for the remainder of the project and after that. Longer-term impact from the project also comes from on-site practical and theoretical training in emerging technologies, and our joint research program allowed the employment of - mostly young - researchers, with which we boost their career opportunities in experimental and computational research methodology.
The iNEXT-Discovery project highlights in many ways that also for the future 'structural biology assisted life science research' will remain a major socio-economic stronghold that keeps on delivering on societal challenges for health, food and biotechnology.
1. In Fragment-based drug discovery, hundreds of small chemicals are being added to “targets” to pick up compounds that interfere with function. FBDD is a flagship access service for our facility users, and for maximizing its output we developed novel software tools that allow the evaluation of an enormous amount of experimental data in real-time. Moreover, a new open data repository for storing complete fragment screening campaigns is being developed in a shared effort with PDBe, the well-known Protein Data Bank in Europe.
2. Another exciting focal point of our internal research program is to increase the throughput of data acquisition and analysis for upcoming structural biology technologies. Cryo-EM grid preparation and pre-screening of grid ice thickness are now largely automated, as well as cryo-EM and serial crystallographic sample evaluation and data pre-processing.
3. Besides static structures of biomolecules, also their behavior over different time scales and their multiple conformations and dynamics are crucial for understanding biological processes. In iNEXT-Discovery, new methods have been pursued that are being extensively tested and streamlined. The NMR-facilities involved advanced time-resolved NMR, and they generated tools for studying RNA and light-sensitive biomolecules. Emerging protocols also allow kinetic NMR on cell surfaces for studying drug-receptor interactions, and we provided prototype equipment and workflows for using bioreactors for in-cell NMR on living systems.
4. Cellular imaging by structural biology is a strongly upcoming field. For developing this, our partners streamlined Focused Ion Beam milling workflows for cryo-EM and soft X-ray tomography automation, and even managed to correlate these methods with super-resolution fluorescence microscopy. Moreover, tools were prepared that facilitate the straightforward combination of X-ray scattering and solution NMR data to study flexible macromolecules, whereas new solid-state NMR tools were created that allow the study of protein dynamics and can be integrated with cryo-EM analyses.
Overall, the scientific impact of iNEXT-Discovery is already evident from over 140 Open Access publications. These describe our technological structural biology advances and user-driven applications for life sciences, drug development, and so forth, and we know that our output will continue to grow for the remainder of the project and after that. Longer-term impact from the project also comes from on-site practical and theoretical training in emerging technologies, and our joint research program allowed the employment of - mostly young - researchers, with which we boost their career opportunities in experimental and computational research methodology.
The iNEXT-Discovery project highlights in many ways that also for the future 'structural biology assisted life science research' will remain a major socio-economic stronghold that keeps on delivering on societal challenges for health, food and biotechnology.