Project iNEXT

iNEXT – Infrastructure for NMR, EM and X-ray crystallography for translational research

ABSTRACT

Structural biology provides insight into the molecular architecture of cells up to atomic resolution, revealing the biological mechanisms that are fundamental to life. It is thus key to many innovations in chemistry, biotechnology and medicine such as engineered enzymes, new potent drugs, innovative vaccines and novel biomaterials.

iNEXT (infrastructure for NMR, EM and X-rays for Translational research) will provide high-end structural biology instrumentation and expertise, facilitating expert and non-expert European users to translate their fundamental research into biomedical and biotechnological applications. iNEXT brings together leading European structural biology facilities under one interdisciplinary organizational umbrella and includes synchrotron sites for X-rays, NMR centers with ultra-high field instruments, and, for the first time, advanced electron microscopy and light imaging facilities (23 partners). Together with key partners in biological and biomedical institutions, partners focusing on training and dissemination activities, and ESFRI projects (Instruct, Euro-BioImaging, EU-OPENSCREEN and future neutron-provider ESS), iNEXT forms an inclusive European network of world class.

iNEXT joint research projects (fragment screening for drug development, membrane protein structure, and multimodal cellular imaging) and networking, training and transnational access activities will be important for SMEs, established industries and academics alike. In particular, iNEXT will provide novel access modes to attract new and non-expert users, which are often hindered from engaging in structural biology projects through lack of instrumentation and expertise: a Structural Audit procedure, whereby a sample is assessed for its suitability for structural studies; Enhanced Project Support, allowing users to get expert help in an iNEXT facility; and High-End Data Collection, enabling experienced users to take full benefit of the iNEXT state-of-the-art equipment.

CEITECprovides access to high field NMR instruments and to high-end cryo-electron microscopy and tomography equipment, which are a part of CEITEC Core facilites Josef Dadok National NMR Centre and Cryo-Electron Microscopy and Tomography.

PROJECT OBJECTIVES      

1.      Provide simple, single point of contact user access to leading facilities for synchrotron X-ray data collection for macromolecular crystallography (MX) and solution scattering (SAXS), Nuclear Magnetic Resonance (NMR), Electron Microscopy (EM) and Advanced Light Microscopy (ALM) in Europe and also prepare the community for the possibilities offered by the new neutron source, the European Spallation Source (ESS). In total more than 1000 user projects will be provided.

2.      Provide user access to linked integrated Structural Biology methodologies in coordination with the ESFRI project Instruct, moving to common access mechanisms and single sign-on (technology convergence after 18 months).

3.      Enable user access on the basis of translational impact and scientific excellence, without requiring advanced knowledge of structural biology, to encourage access by new communities.

4.      Provide EC-coordinated access for the first time in electron microscopy, electron tomography, and advanced light microscopy, increasing the impact of advanced imaging methods and also linking the in vitro structurally orientated study of macromolecular assemblies and their interaction to in situ studies in cells (90 projects provided).

5.      Provide an easy route into structural biology for new user communities by establishing three levels of access: Structural Audit (comprehensive sample assessment for non-experts); Enhanced Project Support (fully supported access); High-End Data Collection (full control over the most advanced equipment for expert users).

6.      Promote drug discovery and development by enabling broader uptake of ligand fragment screening methods for the discovery of chemical probes and hits by providing for the first time an integrated service where the user simply needs to supply suitable crystals. At least 5 campaigns for fragment-based drug discovery will be provided.

7.      Maintain and extend Europe’s leading international role in Structural Biology by ensuring the access of all European leading labs to the best available instruments.

8.      Promote integration of the infrastructures and expansion to new communities by driving three joint biomedical research activities to improve the delivery of (i) structure-based small molecule inhibitor discovery (ligand screening), (ii) the integrated study of membrane proteins, and (iii) the study of macromolecules and their complexes in cells.

9.      Train new user communitiesin advanced technologies at six geographically dispersed training centres outside the major access provider sites (six training & dissemination workshops will be organized), to expand the user base.

10.     Strengthen the links between industrial and academic structural biologists by creating collaborative networks, training events, and new research opportunities, and specifically showcasing new technologies (e.g. direct electron detectors for electron microscopy), which may be transformative in certain industrial sectors to encourage their rapid uptake