"Based on recently published work from Anderson’s group in Oxford, this proposal aims to develop a new technique for optical imaging of membrane potential in living cells using second-harmonic generation (SHG) microscopy with porphyrin-based dyes. This technology should enable the function of neurons, and other excitable cells, to be monitored in real time, with high spatial resolution, in their native networks. The objectives of this project include (1) the synthesis of new porphyrins that bind efficiently to the plasma membranes of cells, exhibit strong voltage-dependent SHG and which avoid photo-damage and phototoxicity, and (2) the demonstration that these dyes can be used to monitor membrane potential in living cells. Prof. Anderson's group in Oxford has pioneered research into porphyrin-based nonlinear optical dyes for many years, and has great expertise in this area. The Department of Chemistry in Oxford has world-class facilities for this research. Ismael López Duarte will soon complete his PhD in the field of phthalocyanine chemistry, but he has no experience in the synthesis of porphyrins, nor of the design and testing of dyes for biological applications. This Fellowship will give him the opportunity to apply his expertise in synthesis to the creation of useful new biological probes. It will provide him with experience in a new and rapidly growing area of research and enable him to broaden his horizons."