Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Study of eta-eta ' mixing from measurement of B-(s)(0) -> J/psi eta((')) decay rates

A study of B and Bs meson decays into J/ψ η and J/ψ η′ final states is performed using a data set of proton-proton collisions at centre-of-mass energies of 7 and 8 TeV, collected by the LCHb experiment and corresponding to 3.0 fb−1 of integrated luminosity. The decay B0 → J/ψ η′ is observed for the first time. The following ratios of branching fractions are measured: B(B0→J/ψη′)B(B0s→ J/ψη′)=(2.28±0.65 (stat)±0.10 (syst)±0.13 (fs/fd))×10−2,B(B0→ J/ψη)B(B0s→ J/ψη)=(1.85±0.61 (stat)±0.09 (syst)±0.11 (fs/fd))×10−2, where the third uncertainty is related to the present knowledge of fs/fd, the ratio between the probabilities for a b quark to form a Bs or a B0 meson. The branching fraction ratios are used to determine the parameters of η − η′ meson mixing. In addition, the first evidence for the decay Bs → ψ(2S)η′ is reported, and the relative branching fraction is measured, B(B0s→ ψ(2S)η′)B(B0s→ J/ψη′)=(38.7±9.0 (stat)±1.3 (syst)±0.9(B))×10−2, where the third uncertainty is due to the limited knowledge of the branching fractions of J/ψ and ψ(2S) mesons