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RoL:EAGER:DESYN-C3: Engineering Microbial Differentiation

RoL:EAGER:DESYN-C3：工程微生物分化

基本信息

批准号：
1844289
负责人：
Corey Wilson
金额：
$ 30万
依托单位：
Georgia Tech Research Corporation
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1844289&HistoricalAwards=false
关键词：
RoL EAGER DESYN C3 Engineering

项目摘要

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.

人类干细胞可以通过分化的过程变成不同的细胞类型（肌肉、血液、大脑）。把分化想象成细胞进行的一系列计算，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结果，以便进行下一次计算，因此它需要某种类型的永久内存。细菌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，人们将能够决定从饮用水中去除毒素的最佳策略，或生产治疗性疫苗。这个项目将创造细菌的记忆结构，并将评估细菌进行不同计算的能力。该项目将为女性和少数族裔学生提供研究机会。还将举办一个讲习班，培训大学生使用研究技术。这个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、阅读框和终止子），这些结构可以根据刺激迅速重新排列。因此，这种反应将被继承，在产生这种反应的刺激因素消失后仍将持续很长时间。为了使这种发展具有重要意义，必须创建两个或更多不同的开关，以便细胞能够执行逻辑计算，类似于计算机程序，允许两种以上不同的解决方案（例如开或关）。这可能最终导致可扩展遗传记忆结构和动态细胞规划的方案和工作流程的发展。将对适当的子系统进行测试和优化，并将用于构建一个全尺寸的MEMORY结构（即生物计算器）和随后的分化结构，该结构将作为9种合成微生物干细胞的处理单元。该奖项反映了美国国家科学基金会的法定使命，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。