Genetic circuits and genome engineering
We engineer genetic circuits in both prokaryotes and eukaryotes. In doing so, we seek to implement precise biological control, stability and robustness. Some ongoing projects include;
Timing and recording. We use feedback and oscillators to record timing of events in single cells. For example, we use a version of the repressillator to record cell behaviors in the mammalian gut. We also develop oscillators based on new principles to yield different behaviors. Further, we seek to develop genetic circuits that do not rely on transcription and will perform as faster environmental sensors. Together with Mike Springer, we are developing a system for monitoring organism flow within a specific environment.
Signatures of genetic engineering. We are developing living sensors to detect specific DNA sequences in the environment. Here, we modify bacteria to take up DNA from the environment and produce a signal indicating what kind of DNA has been seen.
Genome engineering. We use genome recoding to create recoded organisms that fail to undergo horizontal gene transfer once introduced into the environment. Together with colleagues at JCVI, we are developing a fully synthetic human artificial chromosome for introduction of gene circuits into human cells. And we use protein engineering to develop new methods for introduction of DNA into mammalian cells.
Stirling F, Bitzan L, O’Keefe S, Redfield E, Oliver JWK, Way J, Silver PA. (2017). Rational Design of Evolutionarily Stable Microbial Kill Switches. Mol Cell. 16;68(4):686-697.e3. doi: 10.1016/j.molcel.2017.10.033. Link
Green AA, Kim J, Ma D, Silver PA, Collins JJ, Yin P. (2017). Complex cellular logic computation using ribocomputing devices. Nature. 548(7665):117-121. doi: 10.1038/nature23271. Link
Lau YH, Stirling F, Kuo J, Karrenbelt MAP, Chan YA, Riesselman A, Horton CA, Schafer E, Lips D, Weinstock MT, Gibson DG, Way JC, Silver PA. (2017). Large-scale recoding of a bacterial genome by iterative recombineering of synthetic DNA. Nucleic Acids Res. 45(11 ):6971-6980. doi: 10.1093/nar/gkx415. Link
Brown DM, Chan YA, Desai PJ, Grzesik P, Oldfield LM, Vashee S, Way JC, Silver PA, Glass Jl. (2017). Efficient size-independent chromosome delivery from yeast to cultured cell lines. Nucleic Acids Res. 45(7):e50. doi: 10.1093/nar/gkw1252. Link
Kuo J, Stirling F, Lau YH, Shulgina Y, Way JC, Silver PA. (2018). Synthetic genome recoding: new genetic codes for new features. Curr Genet. 64(2):327-333. doi: 10.1007/s00294-017-0754-z. Link