SFB 1403: Cell Death in Immunity, Inflammation and Disease

细胞死亡是维持组织内环境平衡的重要生物学过程，在动物和植物的宿主-微生物相互作用和病原体防御中起着核心作用。最近发现的溶解细胞死亡的分子控制途径，如坏死性下垂、下垂和铁性下垂，揭示了细胞可以在不同的调节性细胞死亡(RCD)模式之间进行选择，并引发了细胞死亡在组织和组织水平上的后果受到细胞死亡方式的深刻影响的概念。垂死的细胞通过与旁观者细胞进行亲密的交叉对话来调节组织的反应，但目前尚不清楚细胞死亡的类型如何决定这种相互作用的结果。虽然现在人们普遍认为不同的RCD途径具有不同的功能，但我们才刚刚开始了解它们各自的生理作用以及这些作用是如何相互关联的。此外，决定细胞是否、何时和如何死亡的机制以及这对周围组织产生的影响仍然知之甚少。本研究的首要目标是了解各种形式的RCD在组织生理学和病理学中的调节机制以及功能和生理后果，尤其是免疫、炎症和宿主-微生物相互作用。在第一个资助期间，CRC研究人员的合作小组取得了重要发现，极大地促进了我们对动物和植物中不同类型RCD的调节机制的理解。此外，CRC研究人员在阐明RCD的不同途径在免疫、炎症和疾病中的作用以及剖析其潜在机制方面取得了相当大的进展。通过大量的网络、教育和培训活动，我们促进和培育了一个高度协作的跨学科研究社区，使我们的研究中心成为国际上著名的细胞死亡研究中心。在接下来的资助期间，我们将进一步扩大和更新我们的计划，以解决细胞死亡研究中的基本悬而未决的问题。通过提高我们对不同形式的RCD在生物生理学和病理学中的调节和功能的理解，并剖析其潜在的机制，我们最终希望提出新的基于知识的治疗方法，用于治疗患者和重要的经济作物中的细胞死亡相关疾病。

Cell death is a fundamental biological process that is critical for the maintenance of tissue homeostasis and plays a central role in host-microbe interactions and pathogen defence in both animals and plants. The recent discoveries of molecularly controlled pathways of lytic cell death, such as necroptosis, pyroptosis and ferroptosis, revealed that cells can select between different modalities of regulated cell death (RCD) and instigated the concept that the consequences of cell death at the tissue and organismal levels are profoundly affected by the way a cell dies. Dying cells regulate tissue responses by engaging in an intimate cross-talk with bystander cells, yet it remains unclear how the type of cell death determines the outcome of this interaction. While it is now generally accepted that the different RCD pathways have distinct functions, we are only just beginning to understand their respective physiological roles and how these are interlinked with each other. Moreover, the mechanisms determining whether, when and how a cell dies and the effects this exerts on surrounding tissues remain poorly understood. The overarching goal of this CRC is to understand the mechanisms of regulation and the functional and physiological consequences of diverse forms of RCD in organismal physiology and pathology, with particular focus on immunity, inflammation and host-microbe interactions. During the first funding period, collaborative groups of CRC researchers made important discoveries that considerably advanced our understanding of the mechanisms regulating different types of RCD in animals and plants. Moreover, CRC investigators made considerable progress in elucidating the role of different pathways of RCD in immunity, inflammation and disease and dissecting the underlying mechanisms. Through a multitude of networking, educational and training activities, we promoted and fostered a highly collaborative inter-disciplinary research community establishing our CRC as an internationally prominent centre on cell death research. During the next funding period, we will further expand and update our program to address fundamental outstanding questions in cell death research. By advancing our understanding of the regulation and function of the different forms of RCD in organismal physiology and pathology and dissecting the underlying mechanisms, we ultimately aspire to propose new knowledge-based therapeutic approaches for cell death-related diseases in patients and in economically important crops.