Novel mammalian cell-based devices that sense and respond

细胞可以被设计成以可观察的方式对环境刺激做出反应。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，以改善对特定线索做出反应的细胞的设计。这将使设备的设计，从诊断到治疗的各种应用。该项目还将为代表性不足群体的学生提供教育和培训机会。具体而言，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，赋予细胞似乎无穷无尽的传感能力。其中大部分已经通过重新连接天然配体-受体相互作用或进化与正交转导信号传导模块连接的非天然或从头设计的受体来实现。当前基于配体的传感器在系统控制和动态特性方面的性能严格依赖于转导机制。这可能无法准确概括细胞对配体的反应特征和细胞装置的预期功能。为了解决这个问题，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-受体相互作用或发展基于合成受体的设备的需要，并可与现有的基于配体-受体的系统结合使用。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.