RoL:EAGER:DESYN-C3: Engineering Microbial Differentiation

人类干细胞可以通过一个称为分化的过程变成不同类型的细胞(肌肉、血液、脑)。想象一下，分化是细胞进行一系列计算，以确定哪种类型的细胞在体内给定的环境中生存得最好。单元格需要记住前一次计算的答案才能进行下一次计算，因此它需要某种类型的永久存储器。细菌种类不会从一种细胞类型转变为另一种细胞类型，因为它们没有记忆的能力。创造记忆可以让一群细菌计算出问题的最佳解决方案。例如，人们将能够决定去除饮用水中毒素的最佳策略，或者生产治疗性疫苗。这个项目将创造细菌的记忆结构，并将评估细菌执行不同计算的能力。该项目将为女性和代表性不足的少数族裔学生提供研究机会。还将开发一个培训本科生所使用的研究技术的研讨会。该项目的目标是创造遗传记忆。所采取的方法是开发基因结构(例如，启动子、阅读框架和终止子)，这些结构可以对刺激做出快速重排。因此，这种反应将是继承的，在消除了创造它的刺激因素之后仍将持续很长时间。为了使这一发展具有重大意义，必须创建两个或更多不同的开关，使得该单元能够执行类似于计算机程序的逻辑计算，该逻辑计算允许两个以上不同的解决方案(例如，开或关)。这最终可能导致可扩展遗传记忆结构和动态细胞编程的方案和工作流程的开发。将进行适当子系统的测试和优化，并将用于构建完整的存储结构(即生物计算器)和后续的差异化架构，作为九种合成微生物干细胞的处理单元。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Human stem cells can become different cell types (muscle, blood, brain) through a process called differentiation. Imagine differentiation as a series of calculations that the cell performs to determine what type of cell will survive best in a given environment in the body. The cell needs to remember the answer to the previous calculations in order to make the next calculation, so it needs a permanent memory of some type. Bacterial species do not change from one cell type to another because they do not have the capability to remember. Creating memories could allow a population of bacteria to calculate the best solution to a problem. For example, the population would be able to decide the best strategy to remove toxins from drinking water, or to produce a therapeutic vaccine. This project will create bacterial memory structures and will evaluate the ability of the bacteria to perform different calculations. The project will offer female and under-represented minority students research opportunities. A workshop for training undergraduates in the research techniques used will also be developed.The goal of this project is to create genetic memory. The approach taken is to develop genetic structures (e.g., promoters, reading frames and terminators) that can be rapidly rearranged in response to stimuli. The response will therefore be inherited, persisting long after the removal of the stimulus that created it. For this development to be significant, two or more different switches must be created so that the cell is capable of performing logical calculations, similar to computer programs, that allow for more than two distinct solutions (e.g. on or off). This could ultimately lead to the development of schemes and workflows for scalable genetic MEMORY structures and dynamic cellular programming. Testing and optimization of the appropriate subsystems will be conducted and will be used to construct a full-scale MEMORY structure (i.e., a biological calculator) and the subsequent differentiation architectures that will serve as the processing unit for nine varieties of synthetic microbial stem cells.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.