Our research activities fall within 3 main areas: membrane protein folding, protein-detergent interactions and protein fibrillation. In all cases, we study the different steps by which proteins change their structure under different circumstances, whether it be the process of inserting into a membrane or detergent micelle or the assembly into long β-sheet rich protein fibrils or amyloid. We focus on several different issues:
- (1) How do proteins aggregate and lead to diseases such as Alzheimer’s and Parkinson’s but also serve useful purposes in forming bacterial amyloid?
- (2) How do surfactants and biosurfactants affect protein structure, stability and function?
- (3) How are membrane proteins “tuned” to fold in a membrane environment?
Technology: We follow the structural and energetic changes involved in these processes using many different complementary techniques:
- (1) Secondary structure (far UV circular dichroism, Fourier Transform Infrared Spectroscopy)
- (2) Tertiary structure (fluorescence, near-UV circular dichroism)
- (3) Kinetics of these changes (rapid reactions by stopped-flow kinetics, slow reactions over hours-days in plate readers)
- (4) Thermodynamics of structural changes (isothermal titration calorimetry, differential scanning calorimetry)
- (5) The types of aggregates formed during protein aggregation and their
- o size(size separation by field flow fractionation/gel filtration and size quantification by static/dynamic light scattering) and
- o effect on membranes (release of membrane contents)
- (6) Imaging of aggregates and membranes by Atomic Force Microscopy, electron microscopy and Laser Confocal Scanning Microscopy
- (7) Binding of aggregates and proteins to surfaces (quartz crystal microbalance)
- (8) Structures of aggregates and complexes at the nm-level by Small Angle X-ray scattering (with Professor Jan Skov Pedersen, Department of Chemistry) and solid-state NMR (with Professor Niels Chr. Nielsen, Department of Chemistry)