Infrastructures for NMR, EM and X-rays for Translational Research

H2020 INFRAIA 2014/15 Call

• Research Infrastructures for translating research on biological structures into innovation in biomedicine.

• expand the availability of structural biology services (X-ray and neutron scattering, advanced NMR and advanced imaging technologies) to new communities of users, and in particular to scientists with backgrounds other than structural biology, including from SMEs

• benefit translational research in drugs discovery, informed drugs and vaccine design and other fields like biotechnology and biomaterials.

• exploit synergies with relevant ESFRI Infrastructures (such as INSTRUCT, ESS, EUROBIOIMAGING, EU-OPENSCREEN).

Criterion 2 - Impact

Score: 4.50 (Threshold: 3.00/5.00 , Weight: 100.00%) Criterion 1 - Excellence

Score: 5.00 (Threshold: 3.00/5.00 , Weight: 100.00%) Criterion 2 - Impact

Score: 4.50 (Threshold: 3.00/5.00 , Weight: 100.00%) Criterion 3 - Quality and efficiency of the implementation

Score: 4.50 (Threshold: 3.00/5.00 , Weight: 100.00%)

Result: 16 jan 2016

Objectives (1)

• Access to X-ray data collection, NMR, EM, Protein Interactions methods

• Show possibilities of the new neutron source, the European Spallation Source (ESS)

• User access to integrated structural biology methodologies in coordination with the ESFRI project Instruct

• Access is based on translational impact and scientific excellence, no advanced knowledge of structural biology required

• Drug discovery and development: ligand fragment screening methods with users simply supplying suitable crystals

Objectives (2)

• Maintain / extend Europe’s leading role in structural biology: access of all European labs to the best available instruments

• Promote integration / expansion to new communities: joint research activities (JRA)

(i) structure-based small molecule inhibitor discovery (ligand screening)

(ii) the integrated study of membrane proteins

(iii) the study of macromolecules and their complexes in cells

• Training & dissemination workshops will be organized to expand the user base

• Strengthen links between industrial and academic structural biologists:

- collaborative networks

- training events

- new research opportunities

- showcasing new technologies

23 Partners

• Utrecht University • EMBL Grenoble, Hamburg, Heidelberg • Diamond Oxford • CERM – Florence • J.W. Goethe University Frankfurt • Netherlands Cancer Institute Amsterdam • CEITEC – Brno • CSIC – Madrid • FVB-FMP – Berlin • Soleil – Gif-sur-Yvette • MAX IV / Lund University • NeCEN Leiden

• LUMC – Leiden • ESRF – Grenoble • RALF-NMR – Grenoble/Lyon • Instruct – Oxford • Aarhus University • ESS – Lund • ELTE – Budapest • ITQB – Oeiras • Oulu University • Patras University • Weizmann Institute

14 Countries

Transnational Access

• NMR Utrecht, Frankfurt, Florence, Berlin, Brno, Lyon, Grenoble • EM

Brno, Diamond, EMBL-Heidelberg, Leiden, Madrid

• X-rays Diamond, EMBL-Grenoble, EMBL-Hamburg, ESRF, Lund, Soleil

• Macromolecular Interactions Amsterdam, EMBL Heidelberg

Three levels of access

• Structural Audit sample quality assessment for non-experts • Enhanced Support fully supported access for non-experts • High-End Data Collection full control over advanced equipment for expert users

So many modalities...

• Structural Audit - Structural Audit - Mail-in SAXS • Enhanced Support - X-ray structure - NMR data - Cryo-EM sample optimization - Macromolecular interactions - Advanced light imaging - Ligand and fragment screening • High-End Data Collection - Synchrotron data - High-field NMR - High-resolution EM

Basic • PAGE • UV/VIS

Quality • Stability • Aggregation • MALLS

Structure? • SAXS • Crystallisation

• Mail-In Sample to the NKI – Electronic Reporting – No user visits

Structural Audit (NKI)

•1-2 weeks visit for highly interactive project

Macromolecular Interactions (NKI)

MST

ITC

Transient FP

SPR

Access projects

A

• Projects will be reviewed by external international experts - Scientific Excellence of the proposed research theme - Relevance for Translational Research in Health, Biotechnology, or nanomaterials - Scientific Track Record of the team - Technical Feasibility

• Access will have to be transnational (member and associated states)

• EMBL: international organization can accept from any European country

• Access for users -outside- Europe is allowed, but limited to <20%

• Users that publish the results have access, exception for SMEs

Training

• Integrating X-ray crystallography and scattering with electron microscopy

• Bringing together X-rays and neutrons for crystal and solution scattering

• Bridging solution methods: from NMR to X-ray scattering and biophysics

• Structural biology approaches for drug development

• Studying macromolecular assemblies: the toolkit of methods

• Integrated methodologies and approached for structural biology

www.inext-eu.org 1 sept 2015

www.inext-eu.org 1 sept 2015

iNEXT Kickoff October 1-2, Utrecht The Netherlands

Instruct-NL

In 2012, Instruct-NL was established as an Instruct Affiliate Centre. In 2013, the main academic partners of the Instruct-NL became a full Instruct Centre. The former Affiliate Centre remains as an Instruct Network.

Instruct-NL Centre

Instruct-NL Network

Overview of Instruct-NL Centre

Year Project Centre Funding source Amount 2009 Equipment to establish protein facility Protein Facilty NWO (Large investment) 1.7M Euro 2009 Titan Krios to establish NeCEN NeCEN NWO (Large investment) 6.2M Euro 2010 Titan Krios to establish NeCEN NeCEN ERDF (EU

Structurefunds) 5.9M Euro

2010 Solid state DNP-NMR (400/800 MHz) Bijvoet Center NWO (Large investment) 5.7M Euro 2011 Bio-NMR Bijvoet Center EU Infrastructure 1.2M Euro 2012 PRIME-XS Bijvoet Center EU Infrastructure 1.0M Euro 2012 Membership of NL to ESFRI Instruct

(’12-’13) Multiple NWO Chemical Sciences 100k Euro

2012 Proteins@Work: National infrastructure for proteomics

Bijvoet Center NWO (National Roadmap)

13.5M Euro

2012 uNMR-NL: National infrastructure for ultra high resolution NMR (1.2 GHz)

Bijvoet Center NWO (National Roadmap)

18.5M Euro

2014 Membership of NL to ESFRI Instruct (’14)

Multiple Various institutes 50k Euro

Total 53.850k Euro

dr. Hans Wienk iNEXT Project Manager Utrecht University dr. Reinout Raijmakers director Bijvoet Center Utrecht University prof. Rolf Boelens coordinator Utrecht University dr. Tassos Perrakis deputy coordinator NKI, Amsterdam

www.inext-eu.org info@inext-eu.org

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