Reprogramming the Gut
Microbes rarely live in isolation outside the laboratory – they are constantly interacting with other species. These relationships are complex but the resulting microbial communities are capable of more than the sum of the individual organisms, heavily impact evolution, and influence our everyday lives. We seek to understand and engineer novel consortia as well as interface successfully with natural communities. In the lab we focus specifically on interacting with the gut microbiome and constructing microbial consortia dependent on autotroph growth.
The microbes that live in our gut interact extensively with each other and with the host. The gut microbiota mediate several essential processes, including the extraction of energy from food and the production of micronutrients such as vitamins. However, disruptions and imbalances in microbiota composition have been associated with infectious disease, inflammatory bowel diseases, obesity and cancer. The ability to prevent gut dysbiosis and to deliver therapeutics in the gut thus represents an attractive opportunity for medical intervention. We are using the tools of synthetic biology to engineer bacteria that can sense, diagnose and treat disorders while living in the gut. In order to make these devices safe, robust and reliable, we are engineering these living diagnostics and therapeutics as part of microbial consortia that i) are mutually dependent for growth, ii) cannot serve as donors or recipients in horizontal gene transfer and iii) undergo cell death on demand or when they leave the gut.
Kotula JW, Kerns SJ, Shaket LA, Siraj L, Collins JJ, Way JC, Silver PA. (2014). Programmable bacteria detect and record an environmental signal in the mammalian gut. Proc Natl Acad Sci U S A. 111(13), 4838-43. PMID: 24639514
Myhrvold C, Kotula JW, Hicks WM, Conway NJ, Silver PA. (2015). A distributed cell division counter reveals growth dynamics in the gut microbiota. Nature Communications, 6: 10039. PMID: 26615910
David T Riglar, Michael Baym, S Jordan Kerns, Matthew J Niederhuber, Roderick T Bronson, Jonathan W Kotula, Georg K Gerber, Jeffrey C Way, Pamela A. Silver. (2016). Long-term monitoring of inflammation in the mammalian gut using programmable commensal bacteria. BioRxiv. Link
Riglar DT, Giessen TW, Baym M, Kerns SJ, Niederhuber MJ, Bronson RT, Kotula JW, Gerber GK, Way JC, Silver PA. (2017). Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Nat Biotechnol, 35(7):653-658. doi: 10.1038/nbt.3879. Link
Riqlar DT, Silver PA. (2018). Engineering bacteria for diagnostic and therapeutic applications. Nature Reviews Microbial, doi: 10.1038/nrmicro.2017.172. Link
Researchers: David Riglar, Bryan Hsu, Yu Heng Lau, Andy Shumaker, Marika Ziesack, Sasha Naydich, and Suhyun Kim in collaboration with the Gibson lab at the JCVI and the Gerber lab at Brigham and Women’s Hospital.