Are you an EPFL student looking for a semester project?
Work with us on data science and visualisation projects, and deploy your project as an app on top of Graph Search.
Genetically-encoded fluorescent sensors for neuromodulators are increasingly used molecular tools in neuroscience. However, these protein-based biosensors are often limited by the sensitivity of the protein scaffold towards endogenous ligands. Here, we explored the possibility of applying computational design approaches for enhancing sensor sensitivity. Using the dopamine sensor dLight1 as proof of concept, we designed two variants that boost the sensor’s potency (EC50) for dopamine and norepinephrine by up to 5- and 15-fold, respectively. Interestingly, the largest effects were obtained through improved designed allosteric transmission in the transmembrane region of the sensor. Our approach should prove generally useful for enhancing sensing capabilities of a large variety of neuromodulator sensors. Competing Interest Statement T.P. is listed as inventor on a patent application on the sensor technology described in this research. All other authors declare no competing interest.
, ,
Raffaella Buonsanti, Seyedehbehnaz Varandili, James Richard Pankhurst, Valeria Mantella