Coordination Funds

协调基金

• 批准号: 529833808
• 负责人: Professor Dr. Jay Gopalakrishnan, Ph.D.
• 金额: --
• 依托单位: Labor für Zentrosomen- und Zytoskelettbiologie
• 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/529833808?language=en
• 关键词: Coordination; Funds

How cells assemble into tissues and maintain tissue integrity are central questions in biology. Primary cilia project from the surface of most vertebrate cells, where they sense and locally transduce extracellular signals. Primary cilia do not function as static organelles. Instead, they dynamically integrate extracellular input, thereby controlling cell fates and functions during tissue development, maintenance, and remodeling in disease. Primary cilia function relies on i) the dynamic composition of molecules within the cilium, precisely regulated by the ciliary trafficking machinery and gating at the ciliary base, ii) the context-dependent sensing and processing of extracellular stimuli, and iii) the dynamic assembly and disassembly in a cell- and tissue-specific manner. We hypothesize that integrating this triad of primary cilia dynamics is critical to control cellular processes during tissue organization and function. Dissecting how primary cilia dynamics govern tissue organization cannot be addressed by an individual lab but requires a collaborative research effort in a Research Unit (RU) with combined expertise covering ciliary dynamics in different tissue types. Thus, the RU will address the common goal in a joint effort, which goes beyond what could be achieved by individual projects or investigators. Our RU consists of seven projects (P1 to P7). P1, P2, and P3 will define how the dynamics of intraciliary molecules control cell fate, morphogenesis, and tissue organization. P4 and P5 will reveal how extracellular stimuli regulate primary cilia dynamics to control cell fate and function. Finally, P6 and P7 will identify the molecular mechanisms underlying how primary cilia assembly/disassembly dynamics and the changes in ciliary signaling dynamics regulate tissue organization. Importantly, every project covers at least two levels of cilia dynamics, uses 2D cell culture and 3D organoids or in vivo animal models, and employs high-content data and specific hypotheses to gain mechanistic understanding. The RU will also include a Mercator fellow who will provide standardized technological and quantitative procedures to analyze cilia dynamics using imaging. Our common goal is to analyze cilia dynamics across different cells and tissues and uncover common and context-specific mechanisms that regulate tissue development and function. On the long term, our combined efforts will allow to decipher the mechanisms that impair cilia dynamics in ciliopathies, and identify potential therapeutic targets.

细胞如何组装成组织并保持组织的完整性是生物学中的中心问题。初级纤毛从大多数脊椎动物细胞的表面伸出，在那里它们感知并局部抑制细胞外信号。初级纤毛不起静止细胞器的作用。相反，它们动态地整合细胞外输入，从而在疾病中的组织发育、维持和重塑期间控制细胞命运和功能。初级纤毛功能依赖于i）纤毛内分子的动态组成，由纤毛运输机制和纤毛基部的门控精确调节，ii）细胞外刺激的上下文依赖性感测和处理，以及iii）以细胞和组织特异性方式的动态组装和拆卸。我们假设，整合初级纤毛动力学的这三个要素对于控制组织和功能期间的细胞过程至关重要。解剖初级纤毛动力学如何支配组织组织不能由单个实验室解决，而是需要在研究单位（RU）中进行合作研究，并结合不同组织类型中纤毛动力学的专业知识。因此，RU将共同努力实现共同目标，这超出了单个项目或调查人员所能实现的目标。我们的RU包括七个项目（P1至P7）。P1、P2和P3将定义纤毛内分子的动力学如何控制细胞命运、形态发生和组织组织。P4和P5将揭示细胞外刺激如何调节初级纤毛动力学以控制细胞命运和功能。最后，P6和P7将确定初级纤毛组装/拆卸动力学和纤毛信号动力学的变化如何调节组织组织的分子机制。 重要的是，每个项目都涵盖至少两个层次的纤毛动力学，使用2D细胞培养和3D类器官或体内动物模型，并采用高内容数据和特定假设来获得机制理解。RU还将包括一名墨卡托研究员，他将提供标准化的技术和定量程序，使用成像分析纤毛动力学。我们的共同目标是分析不同细胞和组织中的纤毛动力学，并揭示调节组织发育和功能的常见和特定机制。从长远来看，我们的共同努力将有助于破译损害纤毛动力学的机制，并确定潜在的治疗靶点。