URoL:ASC:Synthetic Protocell Communities to Address Critical Sensing Challenges

URoL:ASC:合成原始细胞社区应对关键传感挑战

• 批准号: 2319391
• 负责人: Mark Styczynski
• 金额: $ 222.6万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2319391&HistoricalAwards=false
• 关键词: URoL; ASC; Synthetic; Protocell; Communities

This project will create a tool that can be used by untrained users and without sophisticated equipment to allow diagnosis of medical conditions characterized by the combination of multiple indicator molecules. While some medical conditions can be diagnosed by the level of just a single molecule, most require the measurement of multiple molecules’ levels to enable accurate diagnosis. To address this challenge in a user-friendly manner, this project entails creating a tool that harnesses biology to sense target molecules, combine the information gained from those measurements, and report out patient status to the user. The project uses technology that allows genes to be turned on and off in small droplets that mimic simplified versions of cells. Individual droplets sense an individual molecule and then communicate with another droplet that produces a combined readout. By having each droplet detect a single molecule and exploit a reusable form of communication with other droplets, it makes the tool modular for creation of diagnostics for essentially any set of target molecules. The droplet technology and the combination of proposed approaches for communication and combination of signals are unique and novel. If successfully completed, this project would impact society broadly and help address health and other inequities by enabling assessment and monitoring of nutrition status in developing countries and around the world, helping individuals and improving public health policy.As a proof of principle testbed, the project focuses on the development of a comprehensive diagnostic for zinc deficiency, a condition that is responsible for the deaths of tens of thousands of children under the age of 5 every year. The droplet technology uses aqueous two-phase systems combined with cell-free transcription and translation to create “protocells” that enable the implementation of biological circuits for sensing and signal integration and thus the creation of complex biosensors. Multiple protocells each produce a distinct messenger molecule drawn from nature to enable communication with a separate “receiver” protocell that integrates the signal via a three-hybrid system. By using a common communication and integration framework, individual sensor protocells can be changed to sense different target molecules without impacting the downstream biological computation, which greatly simplifies the creation of new diagnostics for different conditions. An important part of the project will also include efforts to make the protocell platform more efficient and robust for field use. These efforts use the Rules of Life for Building a Synthetic Cell and for Microbiome Interactions and Mechanisms as the basis for the development of a platform that could have a substantial impact on nutritional epidemiology and patient health by virtue of easier access to medical diagnostics. The project also envisions and will entail pursuit of environmental applications of the proposed platform. These efforts, combined with outreach efforts and support for students from groups that are underrepresented in engineering, are expected to have a truly broad impact.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.

该项目将创建一种工具，可由未经培训的用户使用，无需复杂的设备，即可诊断以多种指示分子组合为特征的医疗状况。虽然某些疾病可以通过单个分子的水平进行诊断，但大多数疾病需要测量多个分子的水平才能进行准确的诊断。为了以用户友好的方式应对这一挑战，该项目需要创建一个工具，利用生物学来检测目标分子，联合收割机从这些测量中获得的信息，并向用户报告患者状态。该项目使用的技术允许基因在模拟简化版本细胞的小液滴中打开和关闭。单个液滴感测单个分子，然后与产生组合读数的另一个液滴通信。通过使每个液滴检测单个分子并利用与其他液滴的可重复使用的通信形式，它使该工具模块化，用于创建基本上任何一组靶分子的诊断。液滴技术以及所提出的用于信号的通信和组合的方法的组合是独特的和新颖的。如果成功完成，该项目将对社会产生广泛影响，并通过评估和监测发展中国家和世界各地的营养状况，帮助个人和改善公共卫生政策，帮助解决健康和其他不公平问题。这种疾病每年导致数万名5岁以下儿童死亡。液滴技术使用与无细胞转录和翻译相结合的水两相系统来创建“原始细胞”，从而实现用于传感和信号整合的生物电路，从而创建复杂的生物传感器。多个原始细胞中的每一个都产生一个从自然界中提取的不同的信使分子，以便与一个单独的“接收器”原始细胞进行通信，该原始细胞通过三杂交系统整合信号。通过使用通用的通信和集成框架，可以改变单个传感器原始细胞以感测不同的目标分子，而不会影响下游生物计算，这大大简化了针对不同条件的新诊断的创建。该项目的一个重要部分还将包括努力使原始细胞平台在现场使用时更加有效和强大。这些努力使用构建合成细胞和微生物组相互作用和机制的生命规则作为开发平台的基础，该平台可以通过更容易获得医疗诊断对营养流行病学和患者健康产生重大影响。该项目还设想并将需要对拟议平台的环境应用进行研究。这些努力，再加上推广工作和支持学生的群体，是在工程中代表性不足，预计将有一个真正广泛的影响。这个奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的智力价值和更广泛的影响审查标准。