CAREER: Fluorescent Tools for the Study of Biological Magnesium

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With this CAREER Award, the Chemical Measurement and Imaging Program of the Chemistry Division is funding Professor Daniela Buccella of New York University (NYU) to develop chemical tools for the study of biological magnesium by fluorescence-based techniques. Magnesium(II) is the most abundant divalent ion in most cells and plays numerous roles that are essential for cellular function. Abnormal levels of magnesium have been linked to cardiovascular disease, diabetes, neurodegenerative diseases and cancer. The biochemical basis for the connection between magnesium imbalance and human disease, however, remains partially obscure. This gap in knowledge stems from the scarcity of efficient probes for the direct and selective measurement of biological magnesium(II) with the required spatial and temporal resolutions. To fill this gap, this research project focuses on the development of new molecular probes designed to track the accumulation and speciation of magnesium(II) in cells and tissues by optical imaging, which will facilitate detailed studies of the role of this ion in human health and disease. This CAREER Award also supports efforts toward promoting the pursuit of higher education in Science, Technology, Engineering and Mathematics (STEM) disciplines by providing early exposure to scientific research and college life to female high school students in the New York area, and the development of educational resources to bolster undergraduate science teaching at member institutions of the Faculty Resource Network at NYU serving underrepresented minorities in the sciences.This project focuses on the development of synthetic small-molecule fluorescent indicators for rapid visualization and quantification of various forms of cellular magnesium, seeking improved spatial and temporal resolutions as well as reduced interference from other cations abundant in the cellular milieu. Specific objectives include the development of wavelength ratiometric and lifetime-based fluorescent indicators for the study of metal speciation in the cell, with distinct responses for free and bound forms of the metal, as well as new targeted probes aimed at informing in a time- and position-sensitive manner pools of magnesium(II) ions released from intracellular stores. The educational components of this project include hands-on research experiences through a summer program for high school female students in the New York area, and the development of educational resources emphasizing connections between Chemistry and Biology to be made available to member faculty of the Faculty Resource Network at New York University.