Microenvironmental regulation of muscle homeostasis and its role in musculoskeletal diseases

• Applicants: Professor Dr. Matthias Hammerschmidt; Professor Dr. Gerhard Sengle
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 384170921

Supramolecular networks composed of multi-domain extracellular matrix (ECM) proteins represent intricate cellular microenvironments in the musculoskeletal system that are required to balance tissue homeostasis and direct remodelling. Structural deficiency in ECM proteins results in imbalances in ECM-cell communication which are in turn causative for connective tissue disease. Our hypothesis is that extracellular microfibrillar networks composed of fibrillin microfibril/elastic fibres and collagen VI microfibrils facilitate crucial interactions at musculoskeletal junctions required for ECM-cell communication. In this project, we will address how extracellular microfibrillar networks participate in ECM-cell communication at musculoskeletal junctions. Our studies aim to provide a comprehensive and fundamental understanding of the molecular pathomechanisms caused by mutations in extracellular microfibrillar components which will lay the foundation for future translational approaches of congenital muscular dystrophies and related connective tissue disorders characterized by pronounced muscle weakness.

• DFG Programme: Research Units
• Subproject of: FOR 2722: Novel molecular determinants for musculoskeletal extracellular matrix homeostasis – a systemic approach (M2)