Mimicking Nature to Engineer Better Biosensors

Chemosensing in nature relies on biomolecular switches, biomolecules that undergo binding-induced changes in conformation or oligomerization to transduce chemical information into specific biochemical outputs. Motivated by the impressive performance of these natural “biosensors,” which support continuous, real-time detection in highly complex environments, significant efforts have gone into the adaptation of such switches into engineered chemical sensors [1]. In my presentation, I will provide various examples of how gaining a better understanding of natural biomolecular switches enhances our effort to build more sensitive and specific probes [2]. More specifically, I will present the development of a new versatile DNA-based switch that can be adapted to detect virtually any macromolecular targets with both a fluorescent and electrochemical readout [3]. I will also demonstrate how various strategies used by natural biomolecular switches (cooperativity, ligand sequestration) can be adapted to design new switch-based sensors that display broadened, narrowed, or even more complex dynamic ranges. These optimized new probes will be better suited for various specific sensing applications.

[1] Vallée-Bélisle, A., Plaxco, K.W., Curr. Opin. Struc. Biol. 20 (4), 518-26 (2010)

[2] Vallée-Bélisle, A., Ricci, F., Plaxco, K.W. Proc Natl Acad Sci U S A., 106 (33), 13802-7 (2009); 

[3] Vallée-Bélisle, A., Ricci, F., Xia, F., Plaxco, K.W. Nat Nanotechnol., In revision (2010)