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Synthetic gene circuits that can precisely program cellular behavior have great potential for applications in biotechnology, computation, environmental engineering and medicine. However, constructing synthetic gene circuits with reliable, non-trivial function is extremely difficult. A major challenge is to deal with cellular noise or the stochastic variability in gene expression, which is often due to small numbers of interacting molecules inside the cell. We are exploring general and scalable control strategies that will allow us to realize robust gene circuit function despite cellular noise and external perturbations. We approach this problem by using a combination of experimental and computational techniques.
Past efforts in engineering robust circuit dynamics have focused on the role of feedback regulation. Our work focuses on an alternative yet complementary strategy: cell-cell communication. We are particularly interested in quorum sensing - the cell-cell communication mechanism by which many bacteria sense and respond to changes in their population density. Using a synthetic population control circuit (You et al. Nature 2004;428:868), we recently demonstrated that quorum sensing could be coupled with cell killing to generate integrated, robust population dynamics, despite variability among cells in their phenotype. We are currently investigating whether and to what extent quorum sensing can indeed reduce variability in gene expression, and lead to more robust gene circuit dynamics. Furthermore, we are interested in exploring mechanisms of cell differentiation and developmental pattern formation by engineering gene circuits to program these phenomena in bacteria.
Past efforts in engineering robust circuit dynamics have focused on the role of feedback regulation. Our work focuses on an alternative yet complementary strategy: cell-cell communication. We are particularly interested in quorum sensing - the cell-cell communication mechanism by which many bacteria sense and respond to changes in their population density. Using a synthetic population control circuit (You et al. Nature 2004;428:868), we recently demonstrated that quorum sensing could be coupled with cell killing to generate integrated, robust population dynamics, despite variability among cells in their phenotype. We are currently investigating whether and to what extent quorum sensing can indeed reduce variability in gene expression, and lead to more robust gene circuit dynamics. Furthermore, we are interested in exploring mechanisms of cell differentiation and developmental pattern formation by engineering gene circuits to program these phenomena in bacteria.
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Proceedings of the National Academy of Sciences of the United States of Americano. 17 (2024): e2318380121-e2318380121
ACS synthetic biology (2024)
Zongru Li,Qionghua Shen, Emery T Usher, Andrew P Anderson,Manuel Iburg, Richard Lin, Brandon Zimmer,Matthew D Meyer,Alex S Holehouse,Lingchong You,Ashutosh Chilkoti,Yifan Dai,
Nature microbiologypp.1-15, (2024)
Nature Microbiologypp.1-11, (2024)
Rohan Maddamsetti,Yi Yao,Teng Wang, Junheng Gao, Vincent T. Huang,Grayson S. Hamrick, Hye-In Son,Lingchong You
Nature Communicationsno. 1 (2024): 1-15
Chemno. 6 (2023): 1594-1609
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Nature communicationsno. 1 (2023): 7937-7937
Biophysics Reviewsno. 1 (2023): 011305-011305
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