The calcium ion is the central second messenger of the human body. Every cell uses calcium signals to regulate fundamental physiological processes at the cellular, tissue and organ level through both, ubiquitous and unique cell-specific processes. Consequently, cell-type as well as stimulus-specific calcium signatures reflect a combination of pivotal regulatory processes, encoding spatial and temporal signal patterns. Numerous studies have strongly suggested that common diseases (Volkskrankheiten) are associated with aberrant calcium signals. Common diseases affect systemically important internal organs such as heart, lung, kidney and liver that are challenged by chronic damage from different pathological stimuli encountered in daily life. The organs uniformly react with chronic inflammation and fibrosis (tissue scarring) potentially leading to organ failure. Clinically relevant examples include chronic heart failure, chronic obstructive pulmonary disease, chronic kidney failure, and end-stage liver disease. Common diseases are complex diseases that are associated with an ensemble of risk factors and co-morbidities, in particular arterial hypertension, increased body weight, insulin resistance, and hyperlipidemia. Efficient pharmacological strategies to improve patient care and ultimately to facilitate curing these diseases are desperately needed.

Over the past decades, Saarland University has gained an international reputation in the area of calcium signaling. Based on this we want to establish the proposed Cluster of Excellence. We will focus on determining variations in the calcium signature as an important pathological feature associated with common diseases. Extending “classical” case-control studies we plan to explore calcium signatures in a broad spectrum of individuals ranging from diseased patients over trained and untrained unaffected individuals to (competitive) endurance athletes and to integrate data generated by three interdisciplinary scientific modules into multi-scale models. The proposed cluster of excellence aims at systematically decoding and modulating cellular calcium signatures including analysis of the individual’s genetic setup, which may influence through e.g. genetic variations (i.e. mutation), DNA methylation or micro-RNA regulation a calcium signature in a cell- and organ-specific way. Ultimately, we want to capitalize on these data to develop novel therapeutic strategies with the goal to improve both diagnosis and treatment of patients with common diseases.

 

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