Implementation of reliable feedback and control in engineered circuits is a continuing challenge in synthetic biology.
Recent studies have shown that genetic crosstalk between the engineered circuits and endogenous networks of the host cell can lead to cellular context-dependent effects [ 7, 8].
MazF activity increased the abundance of a set of host-cell transcripts (cluster K3 in Fig. 5c), which sequesters resources away from engineered circuits.
By the robust molecular noise filtering circuit design in Proposition 4, in order to guarantee the positive definite symmetric matrices of P, Q1 and Q2, the engineered circuit kinetic parameters k1 and k2 should be in the range k1 ∈ (0, 1] and k2 ∈ [1, 20].
Here, we present an in vitro paper-based platform that provides an alternate, versatile venue for synthetic biologists to operate and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab.
This fundamental engineering constraint is an obstacle to synthetic biologists because it limits the computational capacity of engineered gene circuits.
Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns.
Resource utilization influences the predictability, function and evolutionary stability of engineered networks and constrains the achievable parameter space for synthetic circuit design4.
Moreover, it will offer invaluable knowledge for the design and construction of engineered microbial consortia for desired functionality, thereby advancing synthetic biology for community-based gene circuit engineering.
