Tango Assay: Rubik is simpler.
Look what have they engineered at Howard Hughes Medical Institute: you need 3 transgenes. Transgene #1 encodes a reporter gene under transcriptional control of an exogenous transcription factor; transgene #2 encodes such transcription factor (#2a) linked to a endogenous receptor (#2b) by an aminoacid linker targeted by an exogenous protease; transgene #3 encodes such endogenous protease (#3a) linked to a protein (#3b) known to bind the (#2b) receptor when it is activated by their ligands. This is Tango Assay:
when your lead drug in exam binds your target #2b receptor, it interacts with the #3b partner protein bringing its twin protease #3a. The protease cuts its cognate aminoacid motif in #2. As a results of such artificial signaling cascade (that emulates Drosophila's Notch receptor) you get the release of a exogenous transcription factor #2a that drives the expression of your favorite #1 reporter gene. This is "The genetic design of signaling cascades to record receptor activation" Barnea et al.
It seems to me. There is a trend to interpret complex systems with complex conceptual design in today's molecular pharmacology. For sure this is geeky, funny, and sexy for mind, so it is worth being mentioned in Reportergene. Nevertheless I don't know whether this would be useful also to understand our inner biology. Managing three transgenes (also transiently) is not a joke. Using strong promoter to express receptors and cognate ones is unphysiological and very, very naive.
Barnea, G., Strapps, W., Herrada, G., Berman, Y., Ong, J., Kloss, B., Axel, R., Lee, K.J. (2008). From the Cover: The genetic design of signaling cascades to record receptor activation. Proceedings of the National Academy of Sciences, 105(1), 64-69. DOI: 10.1073/pnas.0710487105