MIT and Boston University engineers have designed biological cells that, according to an MIT press announcement, can count and remember cellular events using simple circuits in which a series of genes are activated in a specific order. Such circuits, which mimic those found on computer chips, could be used to count the number of times a cell divides, which could be applied to the study of aging or to study a sequence of developmental stages. They could also serve as biosensors to count exposures to different toxins—another potential application for the personal care industry. The team developed two types of cellular counters, both described in the May 29, 2009, issue of Science.
According to the report, the researchers are focusing on designing small circuit components to accomplish specific tasks. "Our goal is to build simple design tools that perform some aspect of cellular function," said Timothy Lu, a graduate student in the Harvard-MIT Division of Health Sciences and Technology (HST) and one of two lead authors of the paper. Ari Friedland, a graduate student at Boston University, is also a lead author of the paper. Co-authors are Xiao Wang, postdoctoral associate at BU; David Shi, BU undergraduate; George Church, faculty member at Harvard Medical School and HST; and James Collins, professor of biomedical engineering at BU.
To demonstrate the concept, the team built circuits that count up to three cellular events. In theory, the counters could go much higher. The first counter, dubbed the riboregulated transcriptional cascade (RTC) counter, consists of a series of genes, each of which produces a protein that activates the next gene in the sequence. With the first stimulus, such as an influx of sugar into the cell, the cell produces the first protein in the sequence, an RNA polymerase. During the second influx, the first RNA polymerase initiates production of the second protein, a different RNA polymerase. The number of steps in the sequence is, in theory, limited only by the number of distinct bacterial RNA polymerases.
"Our goal is to use a library of these genes to create larger and larger cascades," said Lu, in the report. The counter's time scale is minutes or hours, making it suitable for tracking cell divisions. Such a counter would be potentially useful in studies of aging or for studying the unfolding of events that occur during embryonic development. Other potential applications include programming cells to act as environmental sensors for pollutants such as arsenic. Engineers would also be able to specify the length of time an input needs to be present to be counted, and the length of time that can fall between two inputs so they are counted as two events instead of one.
"There's a lot of concern about engineered organisms—if you put them in the environment, what will happen?" said Collins in the report, who is also a Howard Hughes Medical Institute investigator. According to him, these counters "could serve as a programmed expiration date for engineered organisms."
The research was funded by the National Institute of Health Director's Pioneer Award Program, the National Science Foundation FIBR program, and the Howard Hughes Medical Institute.