Novel mammalian cell-based devices that sense and respond

基于哺乳动物细胞的新型感知和响应设备

• 批准号: 2036109
• 负责人: Laura Segatori
• 金额: $ 42.57万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036109&HistoricalAwards=false
• 关键词: Novel; mammalian; cell; based; devices

Cells can be engineered to respond in observable ways to environmental stimuli. These cells can be embedded into devices that can quantify the signal generated by the cell response. The goal of this project is to develop cell engineering strategies to improve the design of cells that respond to specific cues. This will enable the design of devices for a variety of applications from diagnostic to therapeutic. This project will also provide educational and training opportunities to students belonging to underrepresented groups. Specifically, training, research, and mentoring opportunities will be offered to high school teachers and students from the Greater Houston area. Receptor engineering has created innovative approaches to endow cells with seemingly endless sensing capabilities. Most of this has been accomplished by rewiring native ligand-receptor interactions or evolving non- native or de novo designed receptors linked to orthogonal transduction signaling modules. The performance of current ligand-based sensors – in terms of system control and dynamic properties – is strictly dependent on the mechanism of transduction. This may not recapitulate accurately the features of the cellular response to the ligand and the intended function of the cellular device. To address this issue, synthetic biology strategies to engineer cellular devices that generate user-defined outputs will be explored. This approach could dramatically change the way cellular devices that sense and respond to the environment are designed. The resulting strategy can be applied to virtually any process associated with a transcriptional response. This would eliminate the need to rewire ligand-receptor interactions or evolve synthetic receptor-based devices, and may be used in combination with existing ligand-receptor based 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.

细胞可以被改造成以可观察的方式对环境刺激作出反应。这些细胞可以嵌入到可以量化细胞反应产生的信号的设备中。该项目的目标是开发细胞工程策略，以改进对特定线索作出反应的细胞的设计。这将使从诊断到治疗的各种应用的设备设计成为可能。该项目还将为属于代表性不足群体的学生提供教育和培训机会。具体来说，培训、研究和指导机会将提供给来自大休斯顿地区的高中教师和学生。受体工程创造了创新的方法，赋予细胞看似无穷无尽的感知能力。这大部分是通过重新连接天然配体-受体相互作用或进化非天然或重新设计的与正交转导信号传导模块相连的受体来完成的。当前基于配体的传感器的性能——在系统控制和动态特性方面——严格依赖于转导机制。这可能不能准确地概括细胞对配体反应的特征和细胞装置的预期功能。为了解决这个问题，我们将探索合成生物学策略来设计产生用户定义输出的细胞设备。这种方法可能会极大地改变感知和响应环境的蜂窝设备的设计方式。由此产生的策略可以应用于几乎任何与转录反应相关的过程。这将消除重新连接配体-受体相互作用或进化合成基于受体的设备的需要，并且可以与现有的基于配体-受体的系统结合使用。该奖项反映了美国国家科学基金会的法定使命，并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，被认为值得支持。

项目成果

The importance and future of biochemical engineering

• DOI: 10.1002/bit.27364
• 发表时间: 2020-05-29
• 期刊: BIOTECHNOLOGY AND BIOENGINEERING
• 影响因子: 3.8
• 作者: Whitehead, Timothy A.;Banta, Scott;Wheeldon, Ian
• 通讯作者: Wheeldon, Ian

Design of Oscillatory Networks through Post-Translational Control of Network Components

• DOI: 10.35534/sbe.2023.10004
• 发表时间: 2023-03
• 期刊: Synthetic biology and engineering
• 作者: Brianna Jayanthi;S. Jayanthi;Laura Segatori