CAREER: Fluorescent Tools for the Study of Biological Magnesium

有了这个职业奖，化学部的化学测量和成像计划资助纽约大学（NYU）的Daniela Buccella教授开发化学工具，通过荧光技术研究生物镁。镁（II）是大多数细胞中最丰富的二价离子，对细胞功能起着许多重要作用。镁含量异常与心血管疾病、糖尿病、神经退行性疾病和癌症有关。然而，镁失衡和人类疾病之间联系的生化基础仍然部分模糊。这种知识上的差距源于缺乏有效的探针，用于直接和选择性地测量生物镁（II）所需的空间和时间分辨率。为了填补这一空白，该研究项目的重点是开发新的分子探针，旨在通过光学成像跟踪细胞和组织中镁（II）的积累和形态，这将有助于详细研究这种离子在人类健康和疾病中的作用。该职业奖还支持通过为纽约地区的女高中生提供早期接触科学研究和大学生活的机会，促进科学，技术，工程和数学（STEM）学科的高等教育，以及开发教育资源，以加强纽约大学教师资源网络成员机构的本科科学教学，为代表性不足的少数民族服务，该项目的重点是开发合成小分子荧光指示剂，用于快速可视化和量化各种形式的细胞镁，寻求提高空间和时间分辨率以及减少细胞环境中丰富的其他阳离子的干扰。具体目标包括开发波长比率和基于寿命的荧光指示剂，用于研究细胞中的金属形态，对游离和结合形式的金属具有不同的响应，以及新的靶向探针，旨在以时间和位置敏感的方式通知从细胞内商店释放的镁（II）离子池。该项目的教育部分包括通过为纽约地区高中女生举办的暑期方案提供实践研究经验，以及开发教育资源，强调化学和生物学之间的联系，供纽约大学教师资源网络的成员教师使用。

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.