Predictable signal amplification with recombinases

New paper out today: "Quantitative characterization of recombinase-based digitizer circuits enables predictable amplification of biological signals." If we ever want to be able to make reliable controller in cells, we need to have well-separated control signals. Many of the biological sensors and other inputs that we work with, however, are really blurry, so we need devices that can clean them up. This paper demonstrates how this can be done in mammalian cells with a circuit that cleans up a poorly separated signal by nearly 3 decibels!

Blurry input (left) is predicted to be separated well by our recombinase device (middle), and that prediction is realized experimentally (right).

This work, part of the NSF Living Computing Project,  involved collaboration across several labs and a lot of work to connect the devices, analytics, and models. Making this work meant really getting down into what we wanted not just biologically but computationally, in terms of the signal properties of the device. The models and metrics guided adjustments in device design that ultimately feed back into a better performing system. I'm personally very happy with the result as an example of a getting really serious about the engineering approach biological systems.