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Infrastructure for NMR, EM and X-rays for translational research

Periodic Reporting for period 3 - iNEXT (Infrastructure for NMR, EM and X-rays for translational research)

Reporting period: 2018-09-01 to 2019-08-31

The main objective of the H2020 project “Infrastructure for NMR, EM and X-rays for Translational Research”, iNEXT, were to make state-of-the-art structural biology research infrastructures available to scientific researchers, which will lead to detailed insight in the mechanism of action of biomolecular complexes in (human) cells. The atomic information for biomolecules (proteins, DNA, hormones, drugs, etc.) and their interactions is of immediate importance for biomedical research, drug discovery and biotechnological development. The research infrastructure contains highly advanced and very large instruments that would be too expensive to setup locally and is operated by expert staff.

Over a period of four years, iNEXT combined Trans-national Access (TA) to a large number of external users (covering their costs for access and travel) with targeted Networking Activities between Partners and external communities in industry and academia, theoretical and practical user training, and strategically designed Joint Research Activities aiding the quantity and quality of these facilities.

Offering trans-national access to high-end structural biology infrastructures has been a long-term success-story that allowed Europe's best researchers to use the best instrumentation. iNEXT has built on the success of previous EU-funding schemes in the past two decades. It integrated for the first time complementary structural biology methodologies in an EU-funded research infrastructure. The consortium provided access to state-of-the-art X-ray synchrotrons and ultra-high field NMR instruments, as well as to new Electron Microscopes, advanced light microscopes and molecular biophysics instrumentation.
"Trans-national Access
Trans-national Access to stimulate translational (biotechnological, biomedical) advances from external users is the central paradigm of iNEXT. In addition to integrative structural biology access for experts, iNEXT set up for first time structural biology access to non-experts to stimulate projects in biomedical and industrial communities. iNEXT allowed continuous submission of projects for individual and combined access modalities, that are organized according to technology and by user experience level. iNEXT offered 13 different access modalities. During the first period these access modalities were opened and their operation monitored, during previous period some were further optimized. More than 900 projects were submitted of which more than 700 were accepted after peer-review. Over 1200 users, mostly from Europe, but also from countries outside the EU, engaged in long- and short-term Trans-national Access at the different iNEXT facilities.

Networking Activities
Numerous activities have been setup to attract users from novel research communities. iNEXT engaged with the biological, biomedical and biotechnological community at large about its activities and structural biology in general. The project functioned as a discussion partner in the European Research Area and mobilized an academic and industrial user community that not only interacted with each other, but also with access-providing partners, funding agencies and the general public. To name a few examples, iNEXT organized Round-Table discussions with representatives of several Biological and Medical Research Infrastructures and health related H2020 projects (e.g. Instruct, West-Life, CORBEL, ELIXIR, IMI, EATRIS, ISBE, EU-OPENSCREEN and others). Also, iNEXT arranged symposia that were part of the large biochemistry FEBS (Federation of European Biochemical Societies) meetings to interact with over 2,500 life science academics. The project contributed a special edition of the journal FEBS Letters with an article on iNEXT research progress. In addition, a workshop was organized that stimulated interactions between researchers from academia and industry. Related to the involvement of industrial parties iNEXT is represented at the PSDI (Protein Structure Determination in Industry) meetings to target many participants from companies. iNEXT partners organized and met at annual iNEXT User Meetings to discuss the projects progress, but also to exchange views with members of its external User Panel, Executive Review Panel and Industrial Platform. At all these meetings users presented their results, whereas also the recent progress from partners was highlighted. Existing and potential users had the opportunity to be trained in contemporary topics during nine topical workshops organized by the iNEXT Training and Dissemination Centers. In addition, during the many trans-national visits, users had opportunities to receive training directly from experts at the infrastructures.

Joint Research Activities
iNEXT had three highly interactive Joint Research Activities to improve access for health and biotech. The activity ""Developing Structure Guided Drug Discovery Workflows"" led to improved workflows for crystal harvesting and X-ray data collection, allowing access to ligand- and fragment-based drug discovery. The research in this activity progressed quickly and led already to novel access opportunities that are in high demand and already heavily oversubscribed by external users. The activity ""Enabling technologies for integral membrane protein systems"" was a crucial, yet challenging endeavor in drug discovery. The research strongly focused on high-throughput structural biology strategies and many protocols have emerged and made public. The activity ""Enabling integrative methodologies for cellular structural biology"" combined in-cell NMR and cryo-EM approaches to provide structural information for proteins and nucleic acids in highly relevant biological systems. Protocols for these have been developed and successfully demonstrated. Also, workflows have been defined to combine cryo-fluorescence microscopy with cryo electron tomography to study cellular structures."
iNEXT enabled open access to high-end structural biology technologies and expertise, thereby strongly stimulating biomedical, biological and biotechnological research in areas with considerable societal needs for development. All major structural biology techniques were made available under a common umbrella, and expert support and on-site training was provided. Direct impact from iNEXT comes from the provision of a wide range of Trans-national Access structural biology opportunities to a community broader than ever before. iNEXT access has focused on innovative and translational aspects, and resulted in many high-impact publications in structural biology, life sciences, drug development (small molecules, vaccines) and biotechnology (engineered enzymes, nano-materials). The long-term impact of iNEXT is imminent from on-site training in emerging technologies and employment of young academics that provides them career opportunities. The life sciences sector in Europe will continue to be a growing socio-economic factor contributing to needs in health, food and biotechnology. The availability of advanced structural biology platforms in iNEXT to a growing life science and biotechnology communities is a crucial asset for innovation in Europe.