Description of research

The research conducted in the section for protein science explores the relationship between the three dimensional structure of the studied macromolecules (proteins and nucleic acids) and their function. For determination of atomic models, we primarily use cryo-electron microscopy and x-ray crystallography supplemented with small angle X-ray scattering. Mass spectrometry is extensively used to for identification of proteins and functional/structural characterization of proteins. Mass spectrometry is also used for biomarker analysis in models of human disease including metabolic, neurodegenerative and inflammatory diseases.

The research of the section involves a broad selection of biological subjects. Examples of topics studied are protein-nucleic acid interaction, cable bacteria, immune system receptors and antibodies, fibrillating proteins, proteolytic enzymes, the extracellular matrix, assembly of cilia, microbial resistance and defense mechanisms, and transmembrane transport of fatty acids, hormones and sugars.

The research in the section also encompass various functional studies complementing the structural studies. This involves e.g. biophysical methods for following protein folding and aggregation, enzymatic reactions and quantification of protein-ligand interactions. Examples of cell based studies conducted in the section are characterization of receptor-ligand interactions and the relationship between the genome and phenotype.

The research is primarily basic science with a wide scope, but some of the results are also used for development of novel drugs. The section is also engaged in contract research with pharmaceutical and biotech companies.

Research areas and projects:

Key technologies within the section:

Structural biology

• Cryo- and negative stain-electron microscopy
• Macromolecular crystallization and diffraction based structure determination
• Small angle X-ray scattering
• Atomic force microscopy (AFM)

Biophysics

• Spectroscopy (fluorescence including plate reader technology, circular dichroism, FTIR, light scattering, stopped-flow kinetics)
• SPR (surface plasmon resonance), BLI (bio-layer interferometry), ITC (isothermal titration calorimetry), surface binding (quartz crystal micro balance), and FIDA (Flow Induced Dispersion Analysis)
• Phospholipid vesicle technology

Protein production and engineering

• Heterologous expression of recombinant proteins in mammalian, yeast and bacteria cells
• Chromatography for purification of soluble and membrane bound proteins
• Selection from antibody, peptide and protein libraries

Mass spectrometry

• Mass spectrometry (MS)-based identification (LC-MS/MS and MALDI-TOF-MS)
• Quantitative MS verification of biomarkers.
• Discovery-based "shot-gun" proteomics (Q-TOF instrument).
• Hydrogen / deuterium exchange MS (Q-TOF instrument)
• Targeted proteomics (quantitative analysis of triple-Q instrument)
• Absolute quantification of proteins by SRM (selected Reaction Monitoring) and QconCAT technology.