Cellular biosensors have several advantages for bio-detection and have proved to be useful as a powerful method for the detection and quantification of a wide range of analytes. However, their application has been limited by the small number of molecules detectable using nature-derived sensors. Here we aim to develop a standard framework for the reliable and predictable engineering of transmembrane receptor with tailored specificity in bacteria. Our aim is to combine synthetic programmable binders termed alphaRep, developed in Philippe Minard’s lab, with engineered receptor cascades developed in Jerome Bonnet’s lab. We want to associate alphaReps as molecular recognition unit with synthetic receptor cascades as signal transducing component. The detection specificity of the bacterial biosensor could be easily modified to meet various applications by simply changing the alphaRep recognition domain. We will start by engineering prototype receptor cascades responding to model ligands and will focus on optimizing the receptor architecture to develop functional and modular detection systems. We will then generate biosensors detecting medically relevant molecules, primarily proteins known as biomarkers of disease and environmental contaminants. These programmable biosensing devices will have a wide range of application in medical diagnosis, environmental monitoring and remediation. Our unique and complementary expertise in experimental synthetic biology and generation of synthetic binders will support the success of our project.