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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
Pauline AUDERGON
isidore@instruct-eric.org

The services listed below are available for access regardless of the call for proposals and research topic you select in your pre-application form.

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
  • Biomolecular complex purification

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

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)
    • SEC-MALS (multi-angle light scattering)

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
  • GC-MS for the analysis of cuticle thickness to test insecticide resistance in mosquitoes

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

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

AlphaFill

AlphaFold models enriched with ligands and co-factors.

  • Alphafill

IMAGING SERVICES

Provided to you by Euro-BioImaging ERIC & VetBioNet

Contact
info@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

All the services listed below are available for access at BSL-1 or BSL-2 regardless of the call for proposals & research topic that you select in your pre-application form.

Preparation of samples at BSL3 might be accommodated as part of the service.

Imaging services that can be provided directly in BSL-3 containment are marked with an *

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)
    • 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.
    • MINFLUX

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

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

Sample Characterization

  • Atomic force microscopy (AFM)


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 & INFRAVEC

Contacts
sequencing-services@isidore-project.eu

The services listed below are available for access regardless of the call for proposals and research topic you select in your pre-application form.

** These services can be provided in combination with or without bioinformatics support.

Genomic sequencing services (microbial / viral DNA/RNA genome)

  • Illumina technology**
  • Oxford Nanopore technology

ISIDORe Services in action

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

Metatranscriptome sequencing services

  • 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

Miscellaneous sequencing services

  • Small RNA Illumina sequencing**
  • Long read DNA sequencing by Nanopore**
  • RNAseq total transcriptome Illumina sequencing**
  • Genotyping of mosquitoes, insecticide resistance and detection of pathogens

ISIDORe Services in action

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