Biosensors for small molecules can be used in applications that range from metabolic engineering to orthogonal control of transcription. Here, we produce biosensors based on a ligand-binding domain (LBD) by using a method that, in principle, can be applied to any target molecule. The LBD is fused to either a fluorescent protein or a transcriptional activator and is destabilized by mutation such that the fusion accumulates only in cells containing the target ligand. We illustrate the power of this method by developing biosensors for digoxin and progesterone. Addition of ligand to yeast, mammalian, or plant cells expressing a biosensor activates transcription with a dynamic range of up to ~100-fold. We use the biosensors to improve the biotransformation of pregnenolone to progesterone in yeast and to regulate CRISPR activity in mammalian cells. This work provides a general methodology to develop biosensors for a broad range of molecules in eukaryotes.DOI: http://dx.doi.org/10.7554/eLife.10606.001

The DLF theory can be understood as an attempt to modify the Standard Model by flexing the Poincare symmetry to certain 7-dimensional symmetries. The D part of the theory is known as Segal’s Chronometry which is based on compact cosmos D=U(2) with the SU(2,2) fractional linear action on it. The oscillator group is viewed as a subgroup LG of the conformal group G=SU(2,2) and certain LG-orbits L in D are studied. We prove existence of such L and of such an embedding of F=U(1,1) into D, that D differs from F by a certain torus whereas D differs from L by a circle on that torus. In the general U(p,q) vs U(p+q) case, the Sviderskiy formula is described - as a tribute to the late Oleg S. Sviderskiy (July 31 1969 – March 30 2011).

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