Development of genetically encoded fluorescent K+ probes

钾离子（K+）在细胞内积累，细胞是生命的最小单位-这是一个过程，对于调节细胞关键功能至关重要。K+穿过可兴奋细胞（如神经元、肌肉细胞和腺细胞）的质膜的通量对于它们的特定细胞功能至关重要。因此，K+稳态的失衡在细胞和生物体水平上具有深远的意义，并且与包括心血管疾病、神经疾病、肌肉疾病和代谢疾病以及癌症在内的多种疾病相关。据推测，在细胞内K+也不均匀地分布在细胞区室之间，并且相应的细胞内K+通量从根本上有助于细胞功能和功能障碍。此外，假设最微小的亚细胞K+信号在细胞生理学和病理学中具有巨大的影响。然而，我们在这方面的理解是非常有限的，由于缺乏合适的方法，使监测K+通量具有高的空间和时间分辨率。该研究项目旨在开发新型的荧光K+生物传感器，可以针对细胞器和细胞亚区。因此，新的荧光探针将能够实时记录局部亚细胞K+信号，因此，将允许研究细胞内K+通量，以获得我们对这种基本离子在健康和疾病中的信号作用的理解。

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.