Studying protein folding using optical tweezers (Modena, Italy)

Advances in single molecule manipulation techniques, such as optical tweezers, have recently made it possible to revisit protein folding with a new approach. In these experiments, molecules are manipulated one at a time and their (un)folding trajectories described in terms of a well-defined reaction coordinate, namely their molecular end-to-end distance. In a recent work, Cecconi et al. described a method to manipulate individual globular proteins with laser tweezers (1). Using this novel experimental approach, Cecconi et al. investigated the folding pathways of single RNase H molecules with unprecedented details, uncovering information inaccessible to more traditional ensemble techniques (2,3). At the Department of Physics of the University of Modena and Reggio Emilia a new line of research has recently been started that focuses on the study of the folding mechanism of single protein molecules using laser tweezers. Individual molecules are mechanically manipulated and their (un)folding trajectories characterized in terms of different parameters, including: i) intermediate states, ii) magnitude of the forces that hold together secondary and tertiary structures, iii) position of the transition states along the (un)folding trajectories, iv) activation energies between different molecular states, v) full free-energy profile of the protein as a function of its extension, vi) diffusion constants of the molecule along the driven coordinate, vii) anisotropy of the energy landscape. We are therefore seeking a motivated postdoctoral research scientist willing to contribute to this research activity. These studies will be carried out using a dual-beam force-measuring laser tweezer set-up recently built at the University of Modena and Reggio Emilia (4). The postdoctoral fellow should have the expertise to master the use of the experimental set-up and possibly improve its performances. The ideal candidate therefore should have a PhD in Physics or related fields and experience with electronic instrumentation and optics. The position is initially available for two years (1 year renewable to a second year upon mutual agreement) and it might be extended subject to the award of further funding. Initial deadline is July 15th 2009, but candidates will be considered until the position is filled. For further details please contact Dr. Ciro Cecconi. Applicants should send their resume (including email address) to ciro.cecconi@gmail.com. 1) Cecconi, C., Shank, E., Marqusee, S., Bustamante, C., “Protein-DNA chimeras for single molecule mechanical folding studies with the optical tweezers.” European Biophysics Journal, 37 (6), 729-738 (2008). 2) Cecconi, C., Shank, E., Bustamante, C., Marqusee, S., “Direct Observation of the Three-State Folding of a Single Protein Molecule.” Science, 309, 2057-2060, (2005). 3) Cecconi, C., Shank, E., Marqusee, S., Bustamante, C., “Studying protein folding with laser tweezers.” Proceedings of the International School Enrico Fermi-Course CLXV, pp.145-160 (Oct 2007). 4) Smith, S.B., Cui, Y.J., and Bustamante, C. 2003. Optical-trap force transducer that operates by direct measurement of light momentum. In Biophotonics, Pt B, pp. 134-162.

Studying protein folding using optical tweezers (Modena, Italy)

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