Instruct-NL

Infrastructure and User Services  

Equipment

The facilities that form Instruct-NL combine a wide variety of specific structural biology equipment and expertise. NeCEN houses the most powerful cryo-Electron Microscopes for life sciences in the Netherlands. The Bijvoet Centre operates several high-field solid and liquid state NMR spectroscopy systems and a large protein mass spectrometry facility. The NKI hosts the Protein Facility, with diverse machinery for (large-scale) protein production, biophysical characterisation of biomolecular interactions, and protein crystallisation.

Experimental services

The Instruct-NL facilities offer the following experimental services to users:

• NeCEN: guided access to cryo-electron microscopy (300 keV Titan Krios 5) 
• Bijvoet Centre: guided access to solid state NMR and solution state NMR (available magnetic field strengths range from 400 to 1200 MHz, some with DNP/cryo-probes for additional sensitivity), and to mass spectrometry for protein characterization, including native MS and proteomics.
• Protein Facility: Guided access to biophysical methods (SPR, ITC, MST, nano-DSF, SEC-MALS, fluorescence-based assays), robotics for 96-well crystallization trials, design of protein expression constructs, protein production in insect and mammalian cells, and automated protein purification (FPLC).

Computational services

For computational structural biology, the following approaches are available via Instruct-NL:

• The Bijvoet Centre developed the HADDOCK software for information driven biomolecular docking.
• The NKI offers services for (crystallographic) protein structure refinement and prediction.

Examples/description of the type of research  

Instruct-ERIC combines all available technologies for structural biology, a scientific discipline that integrates high-tech methods to understand three-dimensional structures and organization of biological molecules, in particular for proteins, nucleic acids and molecular complexes. Researchers in this field develop and use advanced X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, cryo-electron microscopy, biophysical and computational modelling to determine the precise spatial arrangements of atoms within biological macromolecules and systems. Each method delivers unique, often complementary insights, ranging all the way from atomic contacts to molecular interactions, dynamics, and cellular organization. By mapping these properties, structural biology provides the critical understanding of how biomolecules function, interact, and perform complex cellular processes together. Already for many decades, this type of research has been of utmost importance for understanding disease mechanisms at the molecular level, but also for developing new drugs, and to comprehend fundamental biological processes such as enzyme catalysis, cell signalling, and molecular recognition.

In many cases, the ultimate goal that is being pursued by structural biologists is to connect molecular structure with biological function, thereby bridging the gap between molecular details and broader biological systems. For many years, Instruct-NL has been a proper instrument for advertising structural biology, also offering access and training services to all Dutch and international life scientists.

How to access the infrastructure?  

External researchers can request experiments and other services either through the centralized Instruct-ERIC administration system (ARIA) or by getting in direct contact with each of the Instruct-NL facilities. Experiments can be done upon sample shipment, or by in-person visits. All users bring their own final or preliminary samples and can be assisted in data acquisition, analysis, as well as combining the obtained data with other results. More experienced users can receive training in the independent operation of facility equipment; support staff remains always available in the background for handling issues or answering questions.