NIRT: Direct Electronic Sensing of Biomolecular Activity and Signaling

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This award supports a project proposed in response to the Nanoscale Science and Engineering initiative, NSF 03-043, category NIRT. The investigators supported through the award will develop an innovative electronic architecture to construct novel molecular sensors. The architecture will employ carbon nanotube coupled to individual, biologically active molecules such as the myosin light chain kinase (MLCK). Using the electronic signatures generated by kinase recognition and binding events, the interdisciplinary team intends to explore enzymatic activity and biomolecular dynamics at the single molecule limit. At this limit, the electronic signals generated by a particular biomolecular interaction can be unambiguously identified, and the relevant time scales for protein-protein interactions and conformational changes can be directly measured. The real-time, high bandwidth signal acquisition made possible by the nanotube sensor platform enables a search for reproducible electronic signatures from particular biologic interactions. In order to monitor such signals, carbon nanotube circuits will be tailored to incorporate individual MLCK and calmodulin molecules using phage display techniques to isolate and synthesize special molecular agents for effective attachment and transduction. To mitigate the risk that a single approach will fail in reaching the research goal, two complementary sensing architectures will be developed. In one, protein activity will modulate the conductivity of a nanotube-based transistor; in the other, a protein-coated nanotube tip will form an electrochemical electrode. In addition to their research agenda, the investigators aim to initiate and grow an interdisciplinary research group for the education of undergraduate, graduate and postgraduate researchers. This collaborative group will develop a hands-on training environment where student researchers from disparate fields can work together on research projects requiring specializations encompassing nanomaterials synthesis, analytical chemistry, and chemical and molecular biology. The group will also extend a research internship program for high school students, including those from traditionally underrepresented groups. This internship program will build upon successful previous efforts conducted by the investigators at a smaller scale.