Development of genetically encoded fluorescent K+ probes

Potassium ions (K+) accumulate within cells, the smallest units of life - a process, which is essential for the regulation of cellular key functions. K+ fluxes across the plasma membranes of excitable cells such as neurons, muscle- and gland cells are vital for their specific cell functions. Hence, an imbalance of the K+ homeostasis has profound implication at the cellular- and organismal level and is associated with a plethora of diseases including cardio-vascular-, neurological-, muscle-, and metabolic disorders as well as cancer. It is speculated that also within a cell K+ is unequally distributed among cellular compartments and respective intracellular K+ fluxes fundamentally contribute to cell functions and dysfunctions. Furthermore it is hypothesized that tiniest subcellular K+ signals have huge implications in cell physiology and pathology. However, our understanding in this regard is very limited due to the lack of suitable methods that allow monitoring K+ fluxes with high spatial and temporal resolution. This research project aims to develop novel fluorescent K+ biosensors that can be targeted to cellular organelles and subdomains of cells. Accordingly, the novel fluorescent probes will enable real-time recordings of local subcellular K+ signals and, thus, will allow investigating intracellular K+ fluxes to gain our understanding of the signaling role of this fundamental ion in health and diseases.

In this project, we have developed novel fluorescent biosensors that enable precise and sensitive measurement of changes in the concentration of potassium ions ([K+]) in living cells. These nanomachines consist of fluorescent proteins and can be used in cells as well as on cell surfaces and in body fluids. By using these sensors, local changes in [K+] can be detected with high precision for the first time and examined for their effects on signaling and cell metabolism. Such changes are important in neurological defects, metabolic diseases and cancer. By using these sensors, we can learn more about how these diseases work and hopefully find better ways to treat them in the future.