RoL:EAGER:DESYN-C3: Engineering Microbial Differentiation

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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.