Targeted Zinc Photocages for Studying Biological Signaling

通过这一奖项，化学系生命过程化学计划资助伍斯特理工学院的Shawn Buradete博士开发经光诱导反应在细胞中释放锌的螯合剂。金属离子在维持生命的许多过程中扮演着重要的角色。在这些重要的作用中，金属离子携带着使学习、记忆和运动成为可能的信号。虽然钠、钾和钙等金属离子的功能已得到很好的证实，但锌离子的作用，除了它们在特定的锌金属酶中的作用外，还不太清楚。伍斯特理工学院的肖恩·伯德特博士设计并制造了捕捉锌离子的工具，直到光源在所需的时间和位置释放金属离子。该项目将合成化学元素与光谱和生物学方法相结合，以开发新的工具来研究细胞中的锌。几项教育活动被整合到一个计划中，其中包括通过伍斯特智库让在家接受教育的学生参与研究活动。智库项目的学生来自马萨诸塞州伍斯特的多元化社区，那里超过40%的居民属于代表性不足的群体。这一合作努力跨越了传统的科学学科，并利用实践研究经验通过探究来促进化学教学。几十年前，在神经元中发现了囊状锌，但松散结合的锌在信号转导中的许多作用仍然不明确。尽管缺乏明确的机制，但间接证据表明，锌可以调节多种离子通道的活性，并且锌与细胞表面受体的相互作用可能导致多种细胞内反应。研究锌信号转导的主要障碍是缺乏模拟锌在生物系统中波动的空间和时间控制方法。伯德特博士正在通过应用金属络合剂的设计原理来解决这一不足之处，该设计原理具有xanthone和硝基苯乙酸衍生物的光反应性。利用光诱导的脱羧化反应，锌可以在适当的光源下在细胞内释放。该项目提供了研究锌信号的必要工具，并建立了在生物环境中应用这些工具的必要方法。研究目标与教育目标相结合，解决了在家接受教育的学生无法使用实验室设施的问题，但也让这些学生接触到创新研究。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.