MOSBRI offers access to a range of biophysical instruments and methodologies at our partner sites. Below is a list of the all the partners providing TNA. Here you can read about what is offered at each site by selecting the “instrumentation / methodologies offered” drop down link. A link to the full partner description is found to the right of each partner in the list.

TNA partner sites marked with an asterisk (*) offer remote access in the form of sample ship-in services. See the full partner description for details about this offer.

Sites marked with a double asterisk (**) offer remote access in the form of products. See the Products page for a description of what is offered.

1) Pasteur-PFBMI, Molecular Biophysics core facility,
    Institut Pasteur, FR **

Instrumentation / methodologies offered
  • Hydrodynamic characterization of molecular assemblies: Pasteur-PFBMI has developed a multi-approach combination to analyse the macroscopic architecture of molecular assemblies in solution. We offer access to our expertise in complex experimental set-ups and data analysis integration in an ensemble of technologies: next generation analytical ultracentrifugation (AUC), dynamic light scattering (DLS), multi-angle laser light scattering (MALLS), densitometry and viscometry coupled to Taylor Dispersion (TD), allowing to determine accurately physical parameters such as size, shape, mass, intrinsic viscosity, and density. One of our strong points is our capacity to characterize large assemblies (more than 2 partners), including non-protein components such as nucleic acids, glycans, lipids (alone or in complex structures like nanodiscs or extracellular vesicles), detergents and other surfactants.
  • Kinetic characterization of molecular interactions: we have a 25-year experience in the real-time study of biomolecular interactions using different surface plasmon resonance (SPR) and biolayer interferometry (BLI) instruments. Our main specialties are the structure-function characterization of protein-protein interactions and the study of interactions between protein and lipidic structures (liposomes …).
  • Sample quality control and optimization turnkey services for Pasteur-PFBMI TNA users: Prior to other measurements, all samples will undergo quality control. If samples are sent well in advance and do not pass the tests, buffer and storage optimization experiments will be proposed. Our pipeline follows the recognized ARBRE-MOBIEU/P4EU guidelines, and involves DLS, UV-vis spectrophotometry, MALDI-MS, and optionally differential scanning fluorimetry (DSF) and circular dichroism (CD). More information here.

Access modality: Physical access will be for 5 to 10 days on average. Remote access can be considered in exceptional conditions (for instance due to Covid-19 related restrictions).

2) AU-SRCD, SRCD Facility at ASTRID2,
    Aarhus University, DK

Instrumentation / methodologies offered
  • SRCD: High quality CD measurement of liquid or dry-film samples, in a temperature controlled system allowing thermal stability studies.
  • SRLD: A Couette flow linear dichroism (LD) instrument, inducing alignment of long molecules, such as DNA, through the flow of a solution, provides information on the orientation of chromophores of an orientable molecule and of small ligands which may be bound to it.
  • Stopped flow CD measurements: Utilising a small focused beam from the high intensity undulator source on the AU-AMOLine, we also offer access to a unique instrument, rapid-SRCD (rSRCD). Measurements on the millisecond timescale allow the kinetics of rapid secondary structure folding phenomena to be investigated

Access modality: Physical access is allocated as either 2½ or 4 days. Remote access to this facility is provided to industrial users.

Sample requirements

SRCD: Our standard cell for SRCD measurement has a 0.1 mm pathlength and requires about 30 uL loading volume with a typical protein concentration of about 1 mg/ml. The use of salts and buffer containing Cl- ions should be avoided or minimized, as they hinder low wavelength measurements. The optimum buffer is a phosphate buffer, pH adjusted using a mixture of the mono and divalent Na+ forms, with ionic strength adjusted using NaF instead of NaCl. For higher concentration samples, we have shorter pathlength cells readily available. For temperature melts, where the CD spectrum is measured at a range of temperatures, we normally use the 0.1 mm cell with a loading volume of 75-100 uL.

SRLD: The couette flow cell has a pathlength of 0.5 mm and requires a fill volume of 50 uL. The conditions for SRCD required to avoid highly absorbing buffers/salts also apply.

Stopped flow CD measurements: The cell pathlength for these measurements is 2 mm, with a typical starting protein concentration of 0.1 mg/ml required. As multiple shots are required for accurate measurement, ~2 mL of sample is required for a single experiment. The conditions for SRCD required to avoid highly absorbing buffers/salts also apply.

3) ULB – Centre for Structural Biology and Bioinformatics,
    Université Libre de Bruxelles, BE *

Instrumentation / methodologies offered

The main pieces of equipment are:

  • Microarrayer: protein microarrays (up to 4,000 spots/cm2) are produced by an Arrayjet Marathon Microarrayer (ArrayJet, Roslin, UK). Temperature, relative humidity  and HEPA air filtration control provided by a Jetmosphere TM Environmental Control System (ArrayJet, Roslin, UK).
  • Pipetting robot: Pipetting robot Freedom EVO 150 (AirLiha 8) robotic unit from TECAN. Used to prepare 384 well-paltes to feed the microarrayer.
  • FTIR imaging: data are collected using an Agilent 128 x 128 Mercury Cadmium Telluride (MCT) Focal Plane Array (FPA) detector for mid-IR imaging. 15x and 4x objectives + high magnification.
  • Standard FTIR spectroscopy and accessories: five FTIR spectrometers with MCT detectors, ATR, variable angle ATR, polarizers, high throughput 96-well plates transmission FTIR spectroscopy.

Access modality: Typically 3-5 days are sufficient for an exhaustive study of a few samples. Both physical and remote access is provided.

4) LAMBS – Laboratory for Advanced Microscopy Bioimaging Spectroscopy,
    Universita Degli Studi Di Genova, IT *

Instrumentation / methodologies offered

We offer support in project planning, sample preparation, microscope selection and use, image processing, and visualization.

We offer physical and remote access to:

  • AFM-STED, AFM-STORM correlative microscopes
    • Bruker Nanowizard II AFM on a STED Leica TCS STED-CW gated (optimized for green fluorescence)
    • Bruker Nanowizard II AFM on a N-STORM Super-Resolution System on TiE Inverted Microscope and Andor camera iXon 897. 
    • Bruker Nanowizard IV AFM on a STED Leica Stellaris 8 (optimized for red fluorescence.
  • Optical microscopy and spectroscopy: The facility is equipped with different commercial microscopes and a custom made setup.
    • Nikon confocal microscope. (ALMF-IIT) A1R Resonant Confocal System on TiE Inverted Microscope.
    • Nikon confocal and multiphoton resonant scanner microscope, with ISS fast-FLIM module. (ALMF-IIT) A1r MP Multiphoton Confocal System on TiE Inverted Microscope with Okolab incubation system and FLIM capability. 
    • Nikon super resolution system. N-STORM Super-Resolution System on TiE Inverted Microscope and Andor camera iXon 897. 
    • Nikon super resolution system. N-SIM Super-Resolution System on TiE Inverted Microscope with cage incubator system and Andor camera iXon 897. 
    • Olympus Confocal inverted microscope. FV1000 Confocal microscope.
    • Leica Stellaris 8 STED. 
    • Leica Spectral confocal, multiphoton and STED inverted microscope. Leica TCS STED-CW gated and super-continuum excitation. 
    • Genoa Intruments PRISM, image scanning microscopy and fluorescence lifetime super-resolution system.
    • Custom adapted FLIM and MP-STED CW microscope. On Leica TCS STED-CW gated: 
    • Custom made IML-SPIM microscope. 

Access modality: Each access is 5 days long. Both physical and remote access is provided.

5) RUG-BP – Zernike Institute for Advanced Materials,
    Rijksuniversiteit Groningen, NL

Instrumentation / methodologies offered
  • (High Speed) AFM: We provide access to both traditional as well as High speed AFM. Measurements are predominantly performed in liquid.
    Refs: Nature Chemistry, ACS Nano, JACS
  • Optical Tweezers: With this set-up we are able to trap one or two beads and to measure/exert pN forces and nm displacements.
    Refs: Nano Letters, Science Advances
  • ssNMR: The solid state NMR set-up is used for a variety of experiments with a focus on studying self-assembly processes.
    Refs: Nature Communications, JACS 
  • STED microscopy: Our super resolution fluorescence microscopes are both used for fixed cell and life cell experiments.
    Refs: PNAS

Access modality: Access is typically provided as two weeks physical access.

6) EMBL-SPC – Sample Preparation and Characterisation Facility,
    EMBL Hamburg (HH), DE *

Instrumentation / methodologies offered

Biophysical characterization of Integral Membrane Proteins by High-throughput stability screening: Protein stability in detergent or membrane-like environments is the bottleneck for structural studies on integral membrane proteins (IMP). Our pipeline allows high-throughput screening to identify optimal conditions that are suitable for downstream handling during purification. It includes thermal-denaturation assays monitored by differential scanning fluorimetry, static and dynamic light-scattering, and infrared spectroscopy (attenuated total reflection). We have developed screens to identify optimal detergents, buffers and additives for solubilisation. Lipids play a major role in preserving the native environment of eukaryotic membrane proteins and our pipeline helps to detect which lipids or cocktail-lipids are necessary to keep the integrity of IMPs. We address the functionality of membrane transporters by using a setup of solid-supported membrane (SSM) electrophysiology based on the SURFE²R technology for measuring direct transport of substrates across the lipid bilayer.

Interaction studies: We offer a compilation of methods to quantify protein-ligand interaction. This includes isothermal calorimetry, biolayer interferometry (Octet), surface plasmon resonance (Biacore) and differential scanning fluorimetry (nDSF). For the latter technique, we offer an analysis webserver that uses isothermal analysis in order to obtain binding affinities.

Time-resolved studies: This pipeline offers several methods to obtain kinetic information from different read-outs:

  • time-resolved SAXS beamline (P12).
  • stopped-flow device that allows read out of absorbance, fluorescence and fluorescence anisotropy.
  • binding kinetics of surface-immobilized proteins based on biolayer interferometry (Octet).

We offer access to

  • Determination of purity,
  • protein identification and intact mass determination,
  • dispersity analysis,
  • screening of conditions by thermal denaturation assays,
  • protein secondary structure determination and temperature stability by infrared and circular dichroism spectroscopy,
  • FT-IR spectrometry of coated nanoparticles,
  • molecular modelling, and
  • MD simulations and analysis of trajectories.

Access modality: Access is typically allocated as 4 days. Both physical access and remote access are offered.

7) ProLinC – PROtein folding and Ligand INteraction Core facility,
    Linköpings Universitet, SE *

Instrumentation / methodologies offered

Linköping University is the invention site of the SPR application technology Biacore, and continues to develop biosensor methods within Life Science Technologies, where specific sensors can be developed and tailored to user needs. ProLinC holds a full setup of fluorescence techniques, and novel fluorescence probes are designed in-house, with applications to assay amyloid formation based on fluorescence hyperspectral imaging, amyloid fibril seeding kinetic assays, and amyloid fibril polymorph classification assays by fluorescence probes have been developed both for material in tissue (human, mouse, Drosophila) and in vitro. Assays are set up in a normal lab, or in a BSL-3 laboratory for prion studies in accordance with EU regulations.

8) NIC – Molecular Interactions, Department of Molecular Biology
    and Nanobiotechnology, National Institute of Chemistry, SI *

Instrumentation / methodologies offered

We offer access to

  • SPR (Biacore X, Biacore X100, Biacore T200),
  • ITC (MicroCal VP-ITC),
  • MST (Monolith NT.115),
  • Quartz crystal microbalance (OpenQCM),
  • Equipment for protein purification and characterization: circular dichroism, thermofluor, fluorescence and UV/vis spectroscopy, etc.

Access modality: Access is typically allocated for 4 days. Both physical and remote access is provided.

9) ISMB-BIOPHYSX- Protein Crystallography and Biophysics Centre,
    Birkbeck College, University of London, UK *

Instrumentation / methodologies offered

We offer access to:

  • Spectroscopy: Fluorescence with plate reader and anisotropy, UV/Vis double beam, CD, UV/Vis/fluorescence stopped-flow. All spectroscopic instruments are capable of temperature-dependent study from 5-90°C.
  • Molecular interaction detection: BLI, DSF (dual dye/wavelength system supporting soluble and membrane proteins), ITC, DSC.
  • Screening & sizing: Robotic nanolitre pipetting for solution condition screening, DLS and SEC-MALS.

It is expected that most access will be through one of two pipelines:

  • Protein sample optimization: – robotically assisted screening of solution conditions, thermostability screening by DSF, DLS to establish size homogeneity and identify undesirable soluble aggregation. Well-established factorial screens of buffer/detergent/amphipol for soluble and membrane proteins are available. Further study of promising species/conditions by SEC/MALS to enable analysis and isolation of stoichiometrically defined species.
  • Multi-technique interaction studies: Depending on the system and prior knowledge, a combination of interaction methods (BLI/ITC/UV-Vis/FRET/fluorescence) and methods primarily providing structural information (CD/DSC/DLS/SEC-MALS) will be selected to characterize binding events, and detect and understand, or rule out, coupled reactions such as oligomerization or conformational change.

Access modality: Access will be 3-4 days long, with normally two instruments in a pipeline in use simultaneously. Both physical and remote access are provided for protein sample optimization. Multi-technique interactions studies will usually be delivered via physical access.

10) EPR-MRS – EPR-Facility Bioénergétique et Ingénierie des Protéines,
    CNRS & Aix-Marseille University, FR *

Instrumentation / methodologies offered
  • CW EPR: spectrometers working at S, X, Q and W bands (4, 9, 35 and 95 GHz, respectively), T range 1.5-300 K. Bench-top X-band EPR spectrometer (room temperature)
  • Pulse EPR: spectrometer working at X, Q and W bands, T range 1.5-300 K. Arbitrary Wave Generator for microwave pulse shaping. Cryofree system (recycled Helium).
  • Double resonance techniques: ENDOR (X and Q bands), DEER (X, Q and W bands)
  • Sample preparation: redox poising (glove box for sample preparation under anaerobic conditions), grafting of exogenous spin labels (nitroxide spin labels), isotopically labeled samples
  • Data analyses: software and routines, simulations of EPR experimental spectra. Development of dedicated routines (GUI) for specific data processing.
  • More specific expertise: hyperfine interactions and spin-spin coupling analyses to gain high resolution structural data at sub-molecular scale, dynamic properties and long-range organization (inter-label distance measurement) of various biological systems: IDPs, protein complexes, enzymes …
  • NEW pipeline available (June 2022): Redox centre identification, electron transfer and catalytic activities in metalloenzymes and metalloproteins. >>Read more

Access modality: Access is typically allocated for 5 days. Both physical and remote access is available.

11) MoB-IBT – Centre of Molecular Structure,
    Institute of Biotechnology of the Czech Academy of Sciences, CZ *

Instrumentation / methodologies offered
  • ITC, DSC: analytical techniques for the characterization of thermodynamic parameters of biomolecular binding and structural stability of biopolymers
  • nanoDSF: method to analyze the conformational stability of proteins
  • CD: technique for the evaluation of conformation of DNA and secondary structure of proteins
  • MST, SPR: characterization of intermolecular interactions
  • DLS, MADLS, in-drop DLS: determination of particle size
  • Nitrogen glovebox: nanovolume manipulation and sample treatment under defined atmosphere
  • Advanced SAXS: a SAXS instrument (SAXSpoint 2.0 with MetalJet X-ray source) with inline SEC option and in-situ UV-VIS spectrophotometry offering high level sample characterization, with changes monitored spectrophotometrically during exposure
  • Steady-state and time resolved spectroscopy: a FLS1000 photoluminescence spectrometer with picosecond time resolution, and a Vertex 70v Fourier-transform infrared (FTIR) spectrometer with nanosecond time resolution for in-house time-resolved structural biology and biophysics. Femtosecond experiments are available at external facilities (collaboration with the EU infrastructure ELI-Beamlines)
  • Optical tweezers and confocal microscopy: Lumicks C-trap correlative optical tweezers and confocal microscope for single molecule experiments, which offers access to the study of interaction dynamics, providing a unique way of observing and measuring interactions between molecules
  • AUC: Offsite access (individual agreement for a project) is offered for analytical ultracentrifugation at the Charles University in Prague, Faculty of Science

Access modality: Access is offered both as physical and remote access.

12) DSB-UROM – Sapienza University of Rome, IT *

Instrumentation / methodologies offered
  • ARP: Stopped-flow instruments (msec-time frame ≥ 10 ms) to study folding/unfolding processes, enzyme reaction mechanisms, rapid binding or dissociation processes (absorbance and fluorescence). For faster measurements, a Hi-Tech PTJ-64 capacitor-discharge T-jump apparatus ( ≥ 20 μs) for fluorescence and absorbance experiments is available, as well as an in-house built continuous flow (original prototype) based on a capillary mixing methodology (dead-time 50 μs).

The ARP laboratory includes in detail the following equipment:

  • Applied Photophysics single-mixing -SX-18
    • Applied Photophysics Pi-star 180, 
    • Applied Photophysics sequential-mixing DX-17MV
    • Tgk Scientific Hi-Tech PTJ-64 capacitor-discharge T-jump apparatus
    • in-house built continuous flow (original prototype) based on a capillary mixing methodology (dead-time 50 μs) with a fluorescence CCD camera

Spectrofotometers/fluorimeters for general analysis of samples before kinetic measurements are also available.

  • HYP-ACB: The installation uses advanced fluorescent technology for real-time biosensing of energy metabolism (Seahorse Bioscience-Agilent XFE96) in prokaryotic and eukaryotic cells. A hypoxic chamber Don Whitley i2 for measurements up to 3% O2 is available, a feature shared by few other installations in Europe.

The Hyp-ACB laboratory includes the following equipment:

  • Seahorse XFe96 Agilent
    • Hypoxic cabin Don Whitley  mod. i2 Workstation
    • Sterile hood Thermo Scientific MSC Advantage E 1.2
    • Incubator Thermo Scientific FORMA Steri-cycle 250i
    • Microscope EVOS XL CORE Invitrogen
    • Real-Time PCR Applied Biosystems QuantStudio 3

The lab is fully equipped for molecular/cell biology support during experiments.

Access modality: A physical access visit is on average 3 days (ARP) or 5 days (HYP-ACB) long. Each visit comes with 2 or 7 days of remote access for finalizing the experiments, respectively. Remote access can be planned if necessary

13) BIFI-LACRIMA – Institute for Biocomputation and Physics of Complex Systems,
    University of Zaragoza, ES *

Instrumentation / methodologies offered

Protein Stability and Interactions: BIFI-LACRIMA offers equipment for elucidating and assessing protein stability (conformational landscape, equilibrium and kinetic stability of proteins an biologics) and interactions (functional landscape, thermodynamic interaction parameters, cooperative phenomena and allostery), from in vitro assays with isolated protein to cell-based assays:

  • Calorimetry: VP-ITC, Auto-iTC200, VP-DSC, and Auto-PEAQ-DSC (MicroCal, Malvern-Panalytical)
  • Surface plasmon resonance: Biacore T200 (GE Healthcare)
  • Microscale thermophoresis: Monolith NT.115Pico (NanoTemper)
  • Spectroscopy: Chirascan spectropolarimeter (Applied Photophysics), Cary Eclipse fluorimeter (Agilent), NanoStar Dynapro DLS y DynaPro Plate Reader III (Wyatt Technology)
  • Multimode plate readers: FluoDia T70 (PTI), Synergy HT (BioTek), Mx3005p (Agilent), CLARIOStar and FLUOStar (BMG Labtech)
  • Fluorescence microscopy: DMI 6000B (Leica)
  • Single molecule spectroscopy: MicroTime 200 (PicoQuant)

Protein Stabilization and Drug Discovery: LACRIMA is a reference academic laboratory for drug discovery and protein stabilization by applying biophysical, biochemical and computational tools for identifying ligands capable of modulating the function of protein targets and for stabilizing protein targets according to different strategies:

  • stabilization by sequence redesign
  • stabilization for solvent composition optimization (formulation)
  • stabilization by ligand binding
  • target engagement assessment
  • ligand cytotoxicity evaluation

Characterization and Quality control: In addition, basic protein characterization and quality control are available at this facility, e.g.:

  • purity
  • molecular mass
  • molecular size

Access modality: Access is typically allocated for 4-5 days. Both physical and remote access is provided.