My research focuses on how the cell’s architecture influences its metabolism and intracellular signaling and consequently its function. This has been accomplished by the use of experimental methods where the cell’s intracellular organization is maintained and by high-resolution imaging techniques as the electron microscope. Initially, my concern has been to elucidate the role and regulation of local storage of glycogen molecules (the principal storage form of glucose) in specific micro-domains within the cell. Using three different approaches, I and collaborators have shown that the link between glycogen depletion and impaired muscle function most likely originates from a connection between intramyofibrillar glycogen and SR calcium release. This was shown in mechanically skinned rat muscle fibers (Nielsen et al., 2009), isolated human SR vesicles (Ørtenblad et al.,2011), and intact mouse muscle fibers (Nielsen et al., 2014). Interestingly, we have also found that intramyofibrillar glycogen is preferentially depleted during prolonged exercise (Nielsen et al., 2011), which suggests that this could be the explanation for the glycogen-dependent component in the complexity of impaired muscle function during metabolic stress. In perspective, we have found that rodents and humans have almost the same amount of intramyofibrillar glycogen (Nielsen et al. 2014,2015), despite 4-fold differences in total glycogen, indicating a conserved role of intramyofibrillar glycogen across species. List of publications via Pubmed or Web of Science: "Nielsen J AND (Ortenblad N OR Schroder HD OR Vissing K) NOT (Nielsen JS OR Nielsen JH OR Nielsen JB OR Nielsen JL)".