CAREER: Deciphering and Engineering Biological State Machines with Synthetic Biology

职业：用合成生物学破译和工程生物状态机

• 批准号: 1350625
• 负责人: Timothy Lu
• 金额: $ 72.07万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1350625&HistoricalAwards=false
• 关键词: CAREER; Deciphering; Engineering; Biological; State

Biology is full of rich and complex systems where the interplay between past events, present inputs, and genetics determines cellular behavior. For example, stem cells are in a pluripotent "state" in which they can self-renew and also transform into diverse cell types with distinct functions, such as skin, bone, and blood cells, based on the timing and identities of regulatory signals. These properties require cells to store memory and perform computations, similar to modern computers. To understand such systems, the investigator proposes that biological systems can be thought of as state machines, in which the identity and function of a cell as well as transitions between these cell "states" are determined by past events and present inputs. The research team will build synthetic gene circuits that implement artificial biological state machines along with algorithms to guide their design. The research team will experiment on these circuits to quantify and gain insights into their behavior.BROADER IMPACTS. To ensure broad impacts, the investigator will establish a new course called Biological Circuit Engineering Laboratory (BioCEL) to educate interdisciplinary scientists at the intersection of biology and engineering and will provide these teaching materials openly to the public. Furthermore, the investigator will engage high school, community college, and university students with opportunities for hands-on research. The investigator will create competitive games that teach the concepts used in this research to the general public. Finally, the investigator will establish an online resource to share the algorithms and circuits developed in this project to encourage their use by the broader scientific community. The creation of new design strategies for biological state machines is expected to shed insights into natural biological systems and advance important basic science, biotechnology, and biosensing applications.

生物学充满了丰富而复杂的系统，过去的事件，现在的输入和遗传学之间的相互作用决定了细胞的行为。例如，干细胞处于多能“状态”，在这种状态下，它们可以自我更新，也可以根据调节信号的时间和身份转化为具有不同功能的多种细胞类型，如皮肤细胞、骨细胞和血细胞。这些特性要求细胞存储内存并执行计算，类似于现代计算机。为了理解这样的系统，研究人员提出，生物系统可以被认为是状态机，其中细胞的身份和功能以及这些细胞“状态”之间的转换由过去的事件和当前的输入决定。研究小组将建立合成基因电路，实现人工生物状态机沿着算法来指导它们的设计。研究小组将对这些回路进行实验，以量化并深入了解它们的行为。 为了确保广泛的影响，研究人员将建立一个名为生物电路工程实验室（BioCEL）的新课程，以教育生物学和工程学交叉点的跨学科科学家，并将向公众公开提供这些教材。此外，研究人员将让高中，社区学院和大学生有机会进行实践研究。研究人员将创建竞争性游戏，向公众教授本研究中使用的概念。最后，研究人员将建立一个在线资源，以分享该项目中开发的算法和电路，以鼓励更广泛的科学界使用它们。生物状态机的新设计策略的创建有望深入了解自然生物系统，并推进重要的基础科学，生物技术和生物传感应用。