CAREER: Engineering Bacteria Swarming for Biotechnology

职业：为生物​​技术设计细菌群落

• 批准号: 1847356
• 负责人: Tal Danino
• 金额: $ 52.51万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1847356&HistoricalAwards=false
• 关键词: CAREER; Engineering; Bacteria; Swarming; Biotechnology

Synthetic biology is a tool for designing useful coordinated behaviors in bacterial populations. To date, these efforts have focused on modifying E. coli. Other bacteria exhibit more complex behavior than E. coli. One example of this is swarming. E. coli is capable of localized swarming, similar to a flock of birds all flying together in a particular direction. Other bacteria are capable of forming more complex patterns. One example is the formation of periodic ring patterns that can be easily observed visually. The basic idea behind the project is both simple and powerful. If bacteria can be designed to swarm, forming rings in response to a specific signal, the cells can act as a sensor that can be observed easily. The signals could be viruses, toxic chemicals, or dangerous pathogens. These bacteria could then provide a low cost, easily observed method of detection that could be used around the world to help identify and avoid diseases or other toxic agents. The project will also advance STEM education and diversity at several levels. STEM + arts (STEAM) workshops will be developed and run. Students will be recruited to participate in research. In addition, biology-based artworks will be presented to the general public.The objective of this project is to engineer bacterial swarming to generate macroscopic patterns. We hope to create a spatially-encoded biosensor. The first step will be to engineer E. coli gene circuits to create synthetic swarming motility on solid agar. This will help us understand how to control swarming behavior and pattern formation from the bottom-up. A top-down effort will modulate natural swarming behavior in other organ-isms. This will also create a synthetic biology toolkit for these organisms. Finally, these organisms and E. coli will be engineered to record a transient signal by permanently modulating pattern formation. These biosensors will then be applied to the detection of parasites. The biosensor readout will produce patterns at the scale of a Petri dish and easily detectable by eye. Thus, this readout will be invaluable for use in low-resource settings. The complementary bottom-up and top-down approaches will provide fundamental insight into the use of microbial hosts and behaviors as sensors.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.

合成生物学是设计细菌群体中有用的协调行为的工具。到目前为止，这些努力集中在修改E。杆菌 其他细菌表现出比大肠杆菌更复杂的行为。杆菌其中一个例子就是蜂拥而至。E.大肠杆菌能够局部聚集，就像一群鸟一起朝一个特定的方向飞行一样。其他细菌能够形成更复杂的模式。一个例子是周期性的环形图案的形成，可以很容易地观察到视觉。该项目背后的基本思想既简单又强大。如果细菌可以被设计成成群的，根据特定信号形成环，那么细胞就可以充当一个可以很容易观察到的传感器。这些信号可能是病毒、有毒化学物质或危险的病原体。然后，这些细菌可以提供一种低成本，易于观察的检测方法，可以在世界各地使用，以帮助识别和避免疾病或其他有毒物质。该项目还将在多个层面推进STEM教育和多样性。将开发和运行STEM +艺术（STEAM）研讨会。学生将被招募参加研究。此外，生物艺术作品将呈现给公众。这个项目的目标是工程菌群生成宏观模式。我们希望创造一种空间编码的生物传感器。第一步将是工程师E。大肠杆菌基因电路在固体琼脂上产生合成的群集运动。这将帮助我们理解如何自下而上控制群集行为和模式形成。自上而下的努力将调节其他生物体的自然群集行为。这也将为这些生物体创建一个合成生物学工具包。最后，这些生物体和E.大肠杆菌将被改造成通过永久调节模式形成来记录瞬时信号。这些生物传感器将被应用于检测寄生虫。生物传感器读数将产生皮氏培养皿规模的图案，并且容易被眼睛检测到。因此，这一读数对于在资源匮乏的环境中使用将是非常宝贵的。自下而上和自上而下的互补方法将为微生物宿主和行为作为传感器的使用提供基本的见解。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。

项目成果

A DEEP LEARNING PIPELINE FOR SEGMENTATION OF PROTEUS MIRABILIS COLONY PATTERNS

用于分割奇异变形杆菌菌落模式的深度学习流程

• DOI: 10.1101/2022.01.17.475672
• 发表时间: 2022
• 期刊: 2022 IEEE 19th International Symposium on Biomedical Imaging (ISBI
• 作者: Doshi, A;Shaw, M;Tonea, R;Minyety, R;Moon, S;Laine, A;Guo, G;Danino, T.
• 通讯作者: Danino, T.

Engineered bacterial swarm patterns as spatial records of environmental inputs

• DOI: 10.1038/s41589-023-01325-2
• 发表时间: 2023-05-04
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Doshi，Anjali;Shaw，Marian;Danino，Tal
• 通讯作者: Danino，Tal