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ISIDORe project home / Services / Analytical services

Analytical services

Get access to cutting-edge services & technologies for structural biology, imaging & sequencing.

Structural Biology Services

Provided to you by instruct

Contact
Instruct-ERIC
isidore@instruct-eric.org

Nanobody discovery

  • Generation and characterisation of conformational nanobodies (to facilitate the structural analysis of proteins that are notoriously difficult to purify, to crystallize or to study by another method.)
  • Rapid selection of nanobodies by screening/affinity maturation.

Crystallography

  • Crystallisation of Proteins and Nucleic Acids
  • High-throughput Crystallisation
  • CrystalDirect Online Crystallography protein-to-structure pipeline 
  • IceBEAR crystallography pipelines (data management, crystallization, data collection)

ISIDORe Services in action:
Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. doi.org/10.1038/s41467-020-17495-9

Protein production for Structural Biology

  • Protein expression 
  • Cloning 
  • High throughput expression
  • Protein purification

Molecular Biophysics

 Wide range of techniques to study the biophysical characterization of the structure, function and stability of biological macromolecules like proteins, nucleic acids, lipids and their complexes; as well as the kinetic and thermodynamic parameters of their interaction.

  • Circular Dichroism
  • Differential Scanning Fluorescence 
  • Differential Scanning Calorimetry 
  • Dynamic Light Scattering 
  • UV/Vis Spectrometry
  • Microscale Thermophoresis 
  • Surface Plasmon Resonance 
  • High Throughput Biolayer Interferometry 
  • Isothermal titration Calorimetry 
  • Antibody screening in patient sera (Robotein automated Bimolecular analysis platform)

ISIDORe Services in action:
Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes. doi:10.1093/cid/ciab998

Single Molecule and Super-Resolution Microscopy for Structural Biology applications (Instruct)

  • Single-molecule detection with fluorescence microscopy techniques: using widefield microscopy such as TIRF, super-resolution methods SMLM (STORM, GSD/GSDIM, PALM, PAINT)

Mass Spectrometry

  • Native mass spectrometry
  • Single cell mass spectrometry 
  • Proteomic mass spectrometry with possibility for plasma proteome analysis including monitoring of viral and immune response proteins, analysis of single viral proteins and binding to drugs and antibodies
  • Glycan analysis by Mass spectrometry

ISIDORe Services in action:
ICAM-1 induced re-arrangements of capsid and genome prime rhinovirus 14 for activation and uncoating. doi.org/10.1073/pnas.2024251118

Electron Microscopy techniques for Structural Biology

  • Scanning electron microscopy (SEM) 
  • Transmission electron microscopy (TEM)
  • Cryogenic electron microscopy (Cryo-EM)
  • Electron Microscopy Data Processing Services
  • Electron tomography
  • Cryo-Electron tomography
  • Cryo-Correlative Light and EM

ISIDORe Services in action:
Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. doi: 10.1016/j.xcrm.2022.100528
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. doi: 10.1126/science.abd5223

Magnetic Resonance Techniques

  • Solution NMR
  • Solid state NMR
  • Fragment-screening by NMR
  • NMR metabolomic
  • NMR-based screening of protein-drug interactions
  • Glycan analysis by NMR

ISIDORe Services in action:
The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a. doi: 10.1126/sciadv.abm4034
In-Cell NMR Spectroscopy of Functional Riboswitch Aptamers in Eukaryotic Cells. doi:10.1002/anie.202007184

X Ray Structural Biology Techniques

  • X-ray crystallography
  • Biological small angle scattering (Bio-SAXS), 
  • X-ray imaging from synchrotron sources
  • XChem Fragment Screening
  • Fragment screening through automated CrystalDirect Pipeline

ISIDORe Services in action:
The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a. doi: 10.1126/sciadv.abm4034.

PDB-REDO

Procedure to optimise crystallographic structure models, providing algorithms that make a fully automated decision-making system for refinement, rebuilding and validation.

  • PDB-REDO

IMAGING SERVICES

Provided to you by Euro-BioImaging & VetBioNet

Contact
Arina RYBINA
arina.rybina@eurobioimaging.eu

How imaging technologies contribute to understanding viruses
Imaging technologies used to understand COVID-19 infection
Imaging techniques and COVID19 diagnosis
Understanding SARS-CoV-2 replication cycle in human cells

Light Microscopy & Advanced Light Microscopy for Biological Imaging

Fluorescence microscopy

  • Laser scanning confocal microscopy (LSCM/CLSM) 
  • Spinning disc confocal microscopy (SDCM)
  • Light sheet microscopy (LSM) and lattice light sheet microscopy (LLSM)
  • Structured illumination microscopy (SIM)
  • Widefield microscopy: Total internal reflection fluorescence microscopy (TIRF), Deconvolution widefield microscopy (DWM) 
  • Increased resolution confocal microscopy/Image scanning microscopy 
  • Two-Photon Microscopy/Multi-photon microscopy systems

Fluorescence Nanoscopy

  • Stimulated Emission Depletion Microscopy (STED) 
  • Single-molecule localisation microscopy techniques (SMLM): STORM, GSD/GSDIM, PALM
  • Reversible optical fluorescence transitions (RESOLFT)
  • Super-resolution localization microscopy – localization super-resolution experiments (SMLM: dSTORM, GSDIM, STORM, PALM, PAINT), particle tracking, standard wide-field epifluorescence and TIRF microscopy, transmission microscopy.

Functional Imaging and Specialized Technologies

  • High-throughput microscopy (HTM)/High content screening (HCS), RNAi screens 
  • Protein dynamics and interactions (FRET, FCS, FCCS, FLIM, FRAP)
  • Multi-photon microscopy 
  • High resolution episcopic microscopy (HREM)  
  • Photomanipulation
  • High speed imaging
  • Feedback microscopy
  • Cryo-FM

Mesoscopic Imaging

  • Light Sheet mesoscopic imaging: Single-plane illumination microscopy (SPIM), dSLSM
  • Optical projection tomography (OPT)

Label-free Imaging

  • Quantitative phase imaging (QPI)
  • Raman spectroscopy
  • Coherent Anti-Stokes Raman Scattering microscopy (CARS)
  • Mass Spectrometry based Imaging (MSI)

ISIDORe Services in action

3DClusterViSu: 3D clustering analysis of super-resolution microscopy data by 3D Voronoi tessellations. doi:10.1093/bioinformatics/bty200. Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera
doi: 10.1002/bies.202000257

Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies doi.org/10.1016/j.chom.2020.11.003

A spatial multi-scale fluorescence microscopy toolbox discloses entry checkpoints of SARS-CoV-2 variants in Vero E6 cells

Virus morphology: Insights from super-resolution fluorescence microscopy
doi: 10.1016/j.csbj.2021.10.038

Electron microscopy for Biological Imaging / Ultrastructural Analysis in 2D & 3D

  • Scanning electron microscopy (SEM), including 3D SEM of plastic embedded samples
  • Array tomography
  • Focused-ion-beam scanning EM (FIB-SEM)
  • Serial Block Face Scanning EM (SBF-SEM or SBEM)
  • Transmission Electron Microscopy, including Serial section TEM (ssTEM)
  • TEM tomography, STEM tomography
  • Cryogenic electron Microscopy (Cryo-EM: Cryo-ET, Cryo-SEM, Cryo-FIB, Cryo-TEM)
  • Immuno-electron microscopy (immunogold labelling of Tokuyasu cryosections)

ISIDORe Services in action

Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies doi.org/10.1016/j.chom.2020.11.003

SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance doi.org/10.1038/s41467-021-24521-x

Correlative Light Microscopy & Electron Microscopy for Biological Imaging

  • CLEM from live cells to plastic sections (“live” CLEM)
  • Correlative light-electron microscopy from live cells to 3D plastic embedded samples
  • Intravital CLEM
  • High accuracy on section CLEM
  • CLEM on Tokuyasu sections
  • CryoCLEM

ISIDORe Services in action

Post-correlation on-lamella cryo-CLEM reveals the membrane architecture of lamellar bodies doi.org/10.1038/s42003-020-01567-z

Phase contrast X-Ray Imaging

  • Phase contrast X ray imaging (PCI)

ISIDORe Services in action

3D virtual pathohistology of lung tissue from Covid-19 patients based on phase contrast X-ray tomography doi: 10.7554/eLife.60408

Animal imaging (multimodal imaging of small animals)

  • Multimodal imaging of small animals
  • In vivo optical imaging
  • Intravital microscopy
  • Magnetic Resonance Imaging (MRI)
  • Ultra-sound imaging (US)
  • Computed tomography (CT)
  • Nuclear imaging (PET, SPECT)
  • Bimodal technologies
  • Provision of imaging probes/tracers

Animal Monitoring

  • Animal behaviour monitoring
    • Quantitative spatial-temporal monitoring of individual animals and groups using TrackLab or EthoVision XT software (computer vision, UWB, GPS sensors)
    • Computer-aided monitoring: Registration and analysis of manual observations of animals directly or with video feeds/films, potentially including synchronization of data streams, e.g., of physiology by means of The Observer XT
  • Animal physiology monitoring
    • Body temperature (combined with other variables as required), physiology sensors dependent on the animal species and variables required

Histopathology

  • Histopathology

Image Data & Image Analysis

  • Image data analysis
  • AI and Machine Learning (ML)
  • Medical Image Data Archiving

ISIDORe Services in action

Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies doi.org/10.1016/j.chom.2020.11.003

Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera doi: 10.1002/bies.202000257

Sequencing SERVICES

Provided to you by Emergen

Contacts

contact@isidore-project.eu

Common genome sequencing technologies (whole SARS-CoV-2 genome sequencing)

  • Illumina technology, COVIDSEQ strategy, Novaseq sequencer, 750 genomes per lane     , 1500 genomes per run, one run per week
  • Oxford Nanopore technology, ARTIC or MIDNIGHT amplicon strategy, GridIon sequencer, 96 genomes per flow cell, 5 flowcells per instrument, two runs per week
  • Urgent SARS-CoV-2 genome sequencing: Oxford Nanopore technology, Artic strategy, GridIon sequencer, 10 genomes in 8 hours.

ISIDORe Services in action

Evaluation of NGS-Based Approaches for SARS-CoV-2 Whole Genome Characterisation
doi:10.1093/ve/veaa075

Metatranscriptome sequencing

  • Viral metatranscriptomic – Whole genome sequencing of RNA viruses, including SARS-CoV-2 (up to 100 /week)

ISIDORe Services in action

Evaluation of NGS-Based Approaches for SARS-CoV-2 Whole Genome Characterisation
doi:10.1093/ve/veaa075