I-Corps: Cell-free Biosensors

I-Corps：无细胞生物传感器

• 批准号: 2229505
• 负责人: Susan Daniel
• 金额: $ 5万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2229505&HistoricalAwards=false
• 关键词: Corps; Cell; free; Biosensors

The broader impact/commercial potential of this I-Corps project is the development of a platform to isolate and measure activity of transmembrane proteins (TMPs). Transmembrane proteins are one of biology’s most powerful sensing elements as they can detect nearly any chemical or biological compound. For this reason, they are highly sought after for both detection and development of new therapeutics. Roughly 60% of all drug candidates are targeted against transmembrane proteins, including targets such as viral, pain, and immune receptor proteins. Unfortunately, TMPs are challenging to study and use. Currently, scientists and engineers working with transmembrane proteins rely on labor-intensive procedures that require highly specialized equipment and reagents. These requirement result in costly and lengthy research and development that limits the full-scale application of these important biomolecules. The proposed technology may provide a way to expedite this research and allow scientists to bring therapies to market more rapidly.This I-Corps project is based on the development of a rapidly assembled, biosensing platform that uses cell-free technologies to integrate transmembrane proteins into a biomimetic sensing device. Transmembrane proteins are a notoriously difficult class of proteins to study but are catalysts of many biological functions in cells and, therefore, also pharmaceutical targets for disease mitigation. The proposed platform takes a specific gene sequence and directly synthesizes transmembrane proteins into a lipid membrane. This proposed process both provides a native-like environment to mimic the cell and circumvents traditionally difficult synthesis. This proposed cell-free synthesis method allows for an open-box reaction that may be engineered and controlled to produce customized proteins rapidly in a wide range of environments. In addition, this makes it ideal to develop sensing platforms that are highly scalable and tunable, such as integration with microfluidic technologies. Currently, this technology has been demonstrated by synthesizing an ion channel into a biomembrane sensor and using this sensor to detect a small-molecule chemical based on electronic changes. The proposed technology uses advancements in biotechnology and bioelectronics and has the potential to provide the next step in membrane protein biosensing.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.

这个I-Corps项目更广泛的影响/商业潜力是开发一个平台来分离和测量跨膜蛋白（TMP）的活性。 跨膜蛋白是生物学中最强大的传感元件之一，因为它们可以检测几乎任何化学或生物化合物。出于这个原因，它们在检测和开发新疗法方面受到高度追捧。大约60%的候选药物针对跨膜蛋白，包括病毒、疼痛和免疫受体蛋白等靶标。不幸的是，TMP的研究和使用具有挑战性。目前，研究跨膜蛋白的科学家和工程师依赖于劳动密集型程序，需要高度专业化的设备和试剂。这些要求导致昂贵和漫长的研究和开发，限制了这些重要生物分子的全面应用。这项技术可能会加速这项研究，并使科学家们能够更快地将疗法推向市场。I-Corps项目基于快速组装的生物传感平台的开发，该平台使用无细胞技术将跨膜蛋白整合到仿生传感设备中。众所周知，跨膜蛋白是一类很难研究的蛋白质，但它是细胞中许多生物功能的催化剂，因此也是减轻疾病的药物靶点。所提出的平台采用特定的基因序列并直接将跨膜蛋白合成到脂质膜中。这个提议的过程既提供了一个类似天然的环境来模仿细胞，又避免了传统上难以合成的问题。这种提出的无细胞合成方法允许进行开箱反应，该反应可以被工程化和控制以在广泛的环境中快速生产定制的蛋白质。此外，这使得开发高度可扩展和可调的传感平台成为理想选择，例如与微流体技术集成。目前，该技术已经通过将离子通道合成到生物膜传感器中并使用该传感器检测基于电子变化的小分子化学品来证明。这项技术利用了生物技术和生物电子学的进步，有可能为膜蛋白生物传感提供下一步的发展。该奖项反映了NSF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。