[Instructions: Introduce the research area and project objectives. Discuss methods employed, field of impact, collaborations and notable results. Write for an audience of diverse NSE grantees and the wider scientific research community. (At a level roughly equivalent to that of a article in the journal Science.) Use text and figures as appropriate. It is important to include contact information, links, and important references at the end as shown below. ] The primary goal of this research program is to develop hybrid bioelectronic devices with singlemolecule sensitivity. Using an architecture based upon nanoscale conductors directly wired into circuits, these devices may provide new routes for both fundamental and applied nanoscience. The research team aims to fabricate and test biofunctional circuits, and then apply their use to explore enzymatic activity and biomolecular dynamics at the single molecule limit. Figure 1 below schematically depicts a hypothetical single-molecule sensor and captures the promise of different types of science which might be investigated. First, a biomolecule like calmodulin is covalently attached to a nanocircuit (Fig. 1a). Various dynamics of the biomolecule are then electronically monitored, as depicted in Figs. 1b-d. The UCI research team combines a range of interdisciplinary expertise in nanocircuit assembly and testing, the electronic behaviors of circuits in electrolytes, phage display of target and receptor proteins, and the biological interdependence of kinase proteins and their substrates.