Coordination Funds

协调基金

• 批准号: 407145811
• 负责人: Professor Dr. Bent Brachvogel
• 金额: --
• 依托单位: Klinik und Poliklinik für Kinder- und Jugendmedizin
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/407145811?language=en
• 关键词: Coordination; Funds

The FOR2722 research unit has identified novel functions of the ECM across musculoskeletal tissues and gained novel mechanistic insights into connective tissue disorders. Our new discoveries underscore the interdependency between metabolism, secretion pathway-dependent extracellular matrix (ECM) formation and its cellular recognition and recycling. We now hypothesize that a fine-tuned balance between inside-out ECM production and outside-in ECM recognition and remodelling defines musculoskeletal integrity and function across tissues. In the next funding period, the overarching goal of the FOR2722 will be to understand how changes in ECM production, recognition and remodelling can affect the function of musculoskeletal tissues and cause chronic connective tissue disorders. In our four research areas, we will focus on key fundamental questions in musculoskeletal ECM homeostasis emerging from our research in the first funding period: Metabolism - Through which metabolic signalling mechanisms can mtRC dysfunction be translated into disturbed vesicle-mediated ECM secretion and assembly processes in cartilage? Which mechanisms regulate bioavailability and cellular responses of asprosins? Biosynthesis and assembly - To which extent and through which mechanisms are the distinct muscle cell populations affected by mutated collagen VI and how do they contribute to myopathies? How do collagens XII and XIV organize the ECM and the presentation of ECM-encoded bioactive signals to drive neuromuscular development, regeneration and degeneration processes? Cellular communication - Does integrin α11 constitute an invadopodia-associated sensing element of cartilage damage in Fibroblast-like synoviocytes during rheumatoid arthritis and is it linked to their transformation by transmitting signals through collagen fragments into cell-specific alterations that in a perpetuating loop favour further cartilage destruction? How do extracellular microfibrillar networks participate in cell-ECM communication at musculoskeletal junctions? Degradation - How does deficiency or overexpression of Plastin3 disrupt fundamental cellular processes dependent on F-actin dynamics and vesicle trafficking resulting in bone and cartilage ECM-related diseases? Which factors are involved in the onset of osteogenesis imperfecta and can they be targeted to develop suitable new therapies for non-classical osteogenesis patients? How is the reciprocal communication between cells and their ECM fine-tuned at the mechanistic level? It is our overarching goal is to understand how these molecular processes contribute to the onset and progression of musculoskeletal disease and to translate this newly generated knowledge into additional therapeutic options.

FOR2722研究单位在肌肉骨骼组织中确定了ECM的，以及对Tive组织疾病的新机械洞察力（ECM）。在下一个资金期间，识别和重塑骨骼完整性和功能。将关注我们在第一个基金素D中出现的肌肉骨骼ECM稳态中的关键问题：新陈代谢的代谢，将囊泡介导的ECM分泌物转化为MTRC功能障碍，并处理哪些机制和细胞态度？组装受柔蛋白VI影响的独特的肌肉细胞种群是哪些机制，肌病如何？类风湿关节炎期间的滑膜细胞与它们通过胶原蛋白传输信号的转化有关。在W中进行细胞外的微纤维网络参与细胞 - ECM在肌肉骨骼骨骼中的传播中的细胞ECM通信吗？与ECM相关的疾病，他们的成骨剂是对非经典性骨的新疗法的态度吗？是一般的目标是了解分子过程如何促进肌肉骨骼疾病的发作和进展，并将新近生成的知识转化为其他治疗剂。