Biosensors for Protein Aggregation Studies

  • Responsible : Valeria MUSI
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One of the major challenges for the new generation biophotonics is to implement biosensors that can expand our understanding of biological events with important implications in medicine. In particular, we are working on a new research setup aimed at the development of optical sensors applied to biomolecular processes such as protein-protein interactions with a specific interest for protein aggregation. An increasing number of pathologies are associated with the formation of large aggregates, often fibrillar (amyloid) and that contain misfolded proteins, and which are eventually toxic for the organism. Examples of such pathologies, are the Alzheimer and Parkinson diseases, Huntington’s chorea, Creutzfeldt-Jacob disease, cystic fibrosis, Gaucher’s disease, type II diabetes mellitus and the wide group of systemic amyloidosis.

Figure 1. Schematic proposed pathway for protein amyloid fiber formation: partially folded states (misfolded) of a protein self associate leading to oligomer formation and stable amyloid fibers, toxic aggregates for the organism.

Understanding the forces, kinetics and molecular details that lead to protein misfolding and aggregation is therefore a major challenge which potentially requires both a physical and a biochemical approach. An integrated approach is proposed that includes the investigation and use of novel photonic methods to probe the early dynamic events in the aggregation process of proteins. These new biosensor techniques provide a more detailed description of the aggregation kinetics and oligomeric sizes. The control of the progressive formation of the amyloid structures is achieved by biochemical and biophysical methods (chromatographic techniques, optical spectroscopies, FT-IR) classically used for this purpose and available as basic tools for the project.

The laboratory is very well equipped with a FT-IR Spectrometer, Surface Plasmon Resonance Sensors, SNOM, AFM and SEM microscopes as well as analytical techniques for protein purification and characterization.

Figure 2. Fourier transformed Infrared (FTIR) and UV-visible Spectroscopies and Size-exclusion Chromatography equipment.

Actual Projects in this field:

  • SNF project AMY ‘Amyloid oligomer pathogenesis mechanism analyzed by a novel nano-bio spectroscopy based on surface waves resonators’ submitted Sept. 2009
  • SNF project ELF ‘Engineered Local Field’ n°200021-117930