Goal of the project is widening the applicability of electron paramagnetic resonance spectroscopy (EPR) under in-cell conditions. We will work on determining optimum conditions regarding microwave resonator type, and frequency band on the EPR side as well as regarding expression systems and cell types on the biological side. The studies on resonator types will be performed in close collaboration within the priority program “New Frontiers in Sensitivity for EPR Spectroscopy: From Biological Cells to Nano Materials” with the core project of D. Suter. Based on our experience with in-cell EPR on naturally occurring paramagnetic states in proteins containing organic radicals and transition metal center cofactors, we have chosen two specific examples in order to show the relevance of in-cell EPR. The first is the class of blue-light photoreceptors and the second is the class of oxygen tolerant hydrogenases. As a long term goal, together with Suter’s group having the necessary know-how in microresonator technologies an attempt will be made to push in-cell EPR to the limit of single-cell detection.