Targeted Zinc Photocages for Studying Biological Signaling

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With this award, the Chemistry of Life Processes Program in the Division of Chemistry is funding Dr. Shawn Burdette at Worcester Polytechnic Institute to develop chelators that undergo light-induced reactions to release zinc in cells. Metal ions play essential roles in numerous processes that sustain life. Among these important roles, metal ions carry the signals that enable learning, memory, and movement. While the function of metal ions such as sodium, potassium and calcium are well established, the role of zinc ions, save for their role in specific zinc metalloenzymes, is less well understood. Dr. Shawn Burdette of Worcester Polytechnic Institute designs and makes tools that trap zinc ions until a light source releases the metal ion at the desired time and location. This project combines elements of synthetic chemistry with spectroscopic and biological methodologies to develop new tools to study zinc in cells. Several educational activities are integrated into a plan that includes involving home-schooled students in research activities through the Worcester Think Tank. Students in the Think Tank program come from the diverse Worcester, Massachusetts community, where over 40% of the residents belong to underrepresented groups. This collaborative effort crosses traditional disciplines of science and utilizes a hands-on research experience to promote teaching chemistry through inquiry.Vesicular zinc was found in neurons decades ago, but many roles of loosely bound zinc in signal transduction remain ambiguous. Despite the lack of definitive mechanisms, circumstantial evidence suggests zinc can modulate the activity of a variety of ion channels, and zinc interactions with cell surface receptors may lead to a variety of intracellular responses. The central obstacle to studying zinc signaling is a lack of methodologies for mimicking zinc fluctuations in biological systems with spatial and temporal control. Dr. Burdette is approaching this deficiency by applying principles of metal chelator design with the photo-reactivity of xanthone and nitro-phenylacetic acid derivatives. Taking advantage of a light-induced decarboxylation reaction, zinc can be released inside cells with an appropriate light source. This project provides the tools necessary to study zinc signaling as well as establishes the methods necessary to apply those tools in a biological environment. The research objectives are combined with educational objectives that address the lack of access home schooled students have to laboratory facilities, but also exposes those students to innovative research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.