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CAREER: Multi-stimuli Responsive DNA-Nanoshells - Compartmentalizing Molecules at the Nanoscale for Enhanced Reaction Selectivity and Sensitivity

职业：多重刺激响应 DNA 纳米壳 - 在纳米尺度上划分分子以增强反应选择性和灵敏度

基本信息

批准号：
1847869
负责人：
Jessica Rouge
金额：
$ 63.24万
依托单位：
University of Connecticut
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1847869&HistoricalAwards=false
关键词：
CAREER Multi stimuli Responsive DNA

项目摘要

Viruses have evolved self-destruct mechanisms that allow them to release their contents when they are inside the right host. The viruses are decorated with molecules that trigger their degradation when they encounter specific enzymes found within certain biological systems. Using inspiration from how virus particles respond to their environment in highly specific ways, the research group of Professor Jessica Rouge at the University of Connecticut is developing new chemical strategies to synthesize shells of very small size that can both controllably encapsulate small molecules and release them in response to specific stimuli in complex mixtures. Such strategies are important for developing more sensitive biological sensors and more accurate drug delivery systems. This project provides graduate and undergraduate students multidisciplinary research training in nanoscience, chemical synthesis, and biochemistry. In addition, an initiative entitled "Catalyzing Curie-osity" is launched to engage high school teachers and students throughout the state of Connecticut. Through this joint initiative with the UConn Early College Experience program, affordable lab protocols are being designed focusing on the fundamental tools and techniques of bio-nanoscience. These lab modules will be individually tailored to the needs and resources of specific high schools, giving students hands -n experience with this exciting class of nanomaterials and preparing them for future careers related to nanotechnology and chemistry. With the support of the Macromolecular, Supramolecular and Nanochemistry program, the Rouge Group is developing novel chemical crosslinking strategies that can be incorporated into DNA nanomaterials for controlling their assembly and disassembly in complex biological environments. Using a novel DNA-surfactant assembly strategy that generates DNA nanoshells compatible with cells and enzymes, the major goal of this work is to synthesize a combination of peptide and synthetic crosslinkages that can maintain the nanomaterials stability in biological systems while exhibiting selectivity for certain chemical and biochemical stimuli. These stimuli, including temperature and pH changes, or exposure to specific enzyme classes, will be used to gate the release of small molecules for initiating chemical and/or biochemical reactions. Through this work the following goals are addressed: 1) the design of a library of thermoresponsive crosslinkers that enables remotely controlled substrate release, 2) the design of ligand-cargo communication schemes for sensing the local environment of the DNA-nanoshells, and 3) control over solution reaction selectivity via stepwise substrate release from multi-layered peptide crosslinked DNA-nanoshells. Compartmentalization of different substrates within the DNA-nanoshell layers will allow the team to study release rates and subsequent reaction rates of diverse molecules in aqueous systems.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.

病毒已经进化出了自毁机制，当它们进入正确的宿主时，可以释放它们的内容。这些病毒被分子修饰，当它们遇到某些生物系统中发现的特定酶时，这些分子会触发它们的降解。利用病毒颗粒如何以高度特异性的方式对其环境做出反应的灵感，康涅狄格大学的Jessica Rouge教授的研究小组正在开发新的化学策略来合成非常小尺寸的外壳，这些外壳既可以可控地封装小分子，又可以在复杂混合物中响应特定刺激释放它们。这些策略对于开发更灵敏的生物传感器和更精确的药物输送系统非常重要。该项目为研究生和本科生提供纳米科学，化学合成和生物化学的多学科研究培训。此外，还发起了一项题为“催化好奇心”的倡议，以吸引康涅狄格州各地的高中教师和学生。通过与UConn Early College Experience计划的联合计划，正在设计负担得起的实验室协议，重点关注生物纳米科学的基本工具和技术。这些实验室模块将根据特定高中的需求和资源进行单独定制，为学生提供这一令人兴奋的纳米材料课程的实践经验，并为未来与纳米技术和化学相关的职业生涯做好准备。在大分子，超分子和纳米化学计划的支持下，Rouge集团正在开发新的化学交联策略，可以将其纳入DNA纳米材料中，以控制其在复杂生物环境中的组装和拆卸。使用一种新的DNA-表面活性剂组装策略，产生与细胞和酶相容的DNA纳米壳，这项工作的主要目标是合成肽和合成交联的组合，可以保持纳米材料在生物系统中的稳定性，同时对某些化学和生化刺激表现出选择性。这些刺激，包括温度和pH值的变化，或暴露于特定的酶类，将用于门控小分子的释放，以启动化学和/或生物化学反应。通过这项工作，解决了以下目标：1）设计能够远程控制底物释放的温敏交联剂库，2）设计用于感测DNA-纳米壳的局部环境的配体-货物通信方案，以及3）通过从多层肽交联的DNA-纳米壳逐步释放底物来控制溶液反应选择性。DNA纳米壳层内不同基质的分隔将使该团队能够研究水体系中不同分子的释放速率和随后的反应速率。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。