Deciphering the role of secretory pathways in the reciprocal connection between the cellular nutrient sensing machinery and the extracellular matrix

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Cells interact with their environment in a reciprocal manner via surface or secreted proteins. On the one hand, stimuli from the cellular milieu regulate the activity of signalling pathways, and thereby, influence the cellular physiology . On the other hand, cells respond to intra- and extracellular cues by modifying the set of proteins that are actively transported to their surface or secreted into the extracellular space. These include the extracellular matrix (ECM), integrins, receptors, transporters, cytokines and other proteins that mediate key cellular functions such as signalling, intercellular communication, adhesion, chemotaxis, motility and survival. Therefore, inside-out and outside-in processes are part of a functional network that controls cellular homeostasis in health and disease. Here, we aim to investigate the fundamental molecular mechanisms that govern the intricate interplay between nutrient/mTORC1 signalling, cellular metabolism, cargo selection, protein secretion and the ECM. Moreover, in close collaboration with other partners in the consortium, we will study the role of these crucial cellular processes in musculoskeletal homeostasis and disease using relevant cell line models. Collectively, our work will likely have direct translational implications by revealing potential targets for drug development against rheumatoid arthritis, muscle cachexia and other human diseases that manifest with muscle, skeletal, dental or cartilage anomalies.