CAREER: Deciphering and Engineering Biological State Machines with Synthetic Biology

生物学充满了丰富而复杂的系统，在这些系统中，过去的事件、现在的输入和基因之间的相互作用决定了细胞的行为。例如，干细胞处于一种多能“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、骨骼和血细胞。这些特性需要细胞来存储内存和执行计算，类似于现代计算机。为了理解这样的系统，研究者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”之间的转换是由过去的事件和现在的输入决定的。研究小组将构建合成基因电路，实现人工生物状态机以及指导其设计的算法。研究小组将对这些电路进行实验，以量化并深入了解它们的行为。更广泛的影响。为了确保广泛的影响，研究者将建立一个名为生物电路工程实验室（BioCEL）的新课程，以培养生物学和工程学交叉的跨学科科学家，并将这些教材公开提供给公众。此外，调查人员将与高中，社区学院和大学的学生有机会进行实践研究。研究者将创造竞争性游戏，向公众传授这项研究中使用的概念。最后，研究者将建立一个在线资源来分享在这个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揭示自然生物系统的见解，并推进重要的基础科学，生物技术和生物传感应用。

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.