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研究单元已经确定了ECM在肌肉骨骼组织中的新功能，并获得了对结缔组织疾病的新机械洞察力。我们的新发现强调了代谢，分泌途径依赖性细胞外基质（ECM）形成与其细胞识别和回收利用之间的相互依赖性。现在，我们假设内而外的ECM产生与外部ECM识别和重塑之间的微调平衡定义了跨组织的肌肉骨骼完整性和功能。在下一个资金期间，For2722的总体目标是了解ECM产生，识别和重塑的变化如何影响肌肉骨骼组织的功能并引起慢性连接的组织障碍。在我们的四个研究领域中，我们将重点关注肌肉骨骼ECM稳态中的关键基本问题：新代谢 - 代谢 - 代谢信号机制可以通过该研究将MTRC功能障碍转化为分布式的ECM介导的ECM分布式ECM分布式ECM分泌过程，并且是在园林中？哪些机制调节了asprosins的生物利用度和细胞反应？生物合成和组装 - 在哪种程度和通过哪种机制是受突变胶原蛋白VI影响的独特肌肉细胞种群，它们如何对肌病做出贡献？ Collagens XII和XIV如何组织ECM以及ECM编码的生物活性信号的呈现以驱动神经肌肉发育，再生和变性过程？细胞通信 - 整联蛋白α11是否构成了类风湿关节炎期间成纤维细胞样的滑膜细胞软骨损伤的感应元素，它与它们通过胶原蛋白通过胶原蛋白碎片传输信号的转化是否与collage胶的转化有关，该碎片在牢固的loop loop ploop felptuating loop felpectuating loop feloptuctuating loop feed cartialage estialage esterage esterage estsrrape exptrrape;细胞外微纤维网络如何参与肌肉骨骼连接处的细胞ECM通信？降解 - 质子素3的缺乏或过表达如何破坏基本的细胞过程，取决于F-肌动蛋白动力学和蔬菜运输，导致骨骼和软骨ECM相关疾病？在成骨的发作中涉及哪些因素，并且是否可以针对非古典成骨患者开发合适的新疗法？细胞与其ECM之间的相互通信如何在机械水平上进行微调？这是我们的总体目标是了解这些分子过程如何促进肌肉骨骼疾病的发作和进展，并将这些新生成的知识转化为其他治疗选择。