Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure utilize phosphorylation state of a transcription factor to control classifier output. Kinases and phosphatase pairs that function in phosphorylating or dephosphorylating the transcription factor are integrated into the circuit, their expression tuned by the presence of microRNAs of interest (e.g., in a cell). The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

Provided in this disclosure are methods of treating a bacterial infection comprising administering a formulation comprising an antimicrobial peptide described herein when administered to a subject. Further provided herein are methods of treating a bacterial infection wherein the bacterial infection comprises a bacterium with a mutation in a gene resulting in antibiotic resistance.

The invention relates to mammalian cells comprising at least one prokaryotic two-component signaling (TCS) pathway comprised of an activator protein A, a response regulator (RR) protein B activated by said protein A, such activation leading to an activated RR protein B, and an output gene C operably linked to a promoter. Transcription from said promoter is activated by activated RR protein B, and the expression of output gene C defines at least a first state (0, no transcription) and a second state (1, detectable transcription). The invention further relates to logic gates designed from such cells, and methods for integrating a plurality of output signals based on the cells and logic gates of the invention.

A novel technique for reducing the mis-cleavage of the TorA signal peptide, and thereby a method for efficient secretory production of a heterologous protein by a coryneform bacterium using a TorA signal peptide is provided. A coryneform bacterium having an ability of secretory production of a heterologous protein using a TorA signal peptide and has been modified so that the activity of a LepB protein is increased is cultured to produce the heterologous protein by secretory production.

Provided are improved fungal strains and use thereof, wherein the fungal strains are capable of producing an altered level of proteins, enzymes, variants and other substances of interest.

Methods to create two component signal transduction systems by replace the DNA binding domains and output promoters in bacteria are described.

UO.sub.2F.sub.2 biosensors, and related U-sensing and/or F-sensing genetic molecular components, genetic circuits, compositions, methods and systems are described, which in several embodiments can be used to detect and/or neutralize uranium and in particular bioavailable UO.sub.2F.sub.2.

Provided herein are feedback controller circuits and cell state classifiers for tunable phosphorylation-based transcriptional regulation of gene expression in cells based on intracellular miRNA profiles and degradation by small molecules. Also provided are methods of using feedback controller circuits and cell state classifiers for determining the cell state, and methods of treating cells and subjects using feedback controller circuits and cell state classifiers encoding therapeutic output molecules.

Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure utilize phosphorylation state of a transcription factor to control classifier output. Kinases and phosphatase pairs that function in phosphorylating or dephosphorylating the transcription factor are integrated into the circuit, their expression tuned by the presence of microRNAs of interest (e.g., in a cell). The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

A novel technique for improving secretory production of a heterologous protein by coryneform bacteria is described, as well as a method for secretory production of a heterologous protein. A coryneform bacterium is described that has been modified to have a specific mutation so as to harbor a phoS gene, and when cultured, is able to to produce a heterologous protein by secretory production.