"Spectrin domains R15, R16 and R17 are found in tandem arrays in proteins of the cytoskeleton, and spectrin itself is believed to be responsible for maintaining the shape of erythrocites by imparting elasticity to the cell membrane. These three domains share virtually identical structure, stability, contact order, helical propensity, and transition state structure. However, in spite of the striking structural resemblance and the apparently common function, these proteins fold to their native conformation with a speed that varies over more than three orders of magnitude. Why? There is some evidence to suggest that such diversity originates from energy landscape “roughness”. Slow folding domains (R16 and R17) appear to have rough energy landscapes, whereas the fast folding domain R15 has a smooth energy landscape. By means of a novel, single-molecule spectroscopic technique developed by Prof. Benjamin Schuler at the Department of Biochemistry of the University of Zurich, I want to test this hypothesis, investigating directly the energy landscape of these homologous spectrin domains, quantifying the roughness of their energy landscape, and discover its sequence determinants. This research is the first direct investigation of energy landscape roughness of proteins for which this feature is believed to clearly affect the folding rate. These studies could not only result in substantial conceptual progress in the field of protein folding, providing a missing link between theory and experiment, but also lead to further developments of the single-molecule spectroscopy for biophysical investigation in general"