Coordination Funds

dfg研究单元“唾液酸在发育和免疫中的调节作用”的总体目标是在生物体、细胞和分子水平上破译唾液多糖的基本功能。这个研究单位的中心概念是结合分析发育和免疫方面的唾液生物学，以获得洞察他们复杂的相互作用。由于其复杂性，聚糖经常被忽视，但很明显，它们在许多生物和疾病过程中起着关键作用。我们将重点关注由唾液酸覆盖的聚糖，这是一种丰富的聚糖类，其特征是结构多样性巨大。唾液酸是许多细胞通讯过程中的关键成分，是自我识别的关键决定因素。因此，唾液化模式的改变转化为自我识别、组织稳态和免疫耐受的潜在异常改变。由于唾液聚糖的结构复杂性及其在发育和免疫过程中的核心作用，跨学科的方法是必要的，以充分了解唾液聚糖的基本作用。因此，该研究单位结合了发育生物学、免疫学、神经生物学、结构生物学、生物化学和干细胞糖组学的互补专业知识，以有效地解决唾液生物学的关键问题。一套独特的唾液聚糖特异性小鼠模型，糖工具和尖端的分析方法将使我们能够揭示唾液体的多层复杂性如何转化为生物学功能。我们的战略将促进和利用综合方法来促进我们对发育和免疫十字路口过程的理解，如免疫耐受的诱导和维持（例如在胎儿-母体界面），免疫细胞发育和组织稳态的长期维持。第二个筹资期的主要目标是：(i)揭示新的唾液酸在胚胎发育中的功能，（ii）了解唾液聚糖在淋巴细胞发育和功能中的作用，（iii）解剖聚唾液酸在预防自身免疫中的作用，（iv）探索聚唾液酸识别免疫受体的结构和功能，(v)了解聚唾液酸-趋化因子相互作用及其生物学功能，（vi）确定唾液酸o -乙酰化的功能作用。我们期望我们的研究项目将为唾液聚糖的功能提供新的见解，这将有助于更好地了解聚糖在妊娠并发症以及自身免疫性和年龄相关炎症性疾病发展中的影响。

The overall goal of the DFG-Research Unit “Sialic Acid as Regulator in Development and Immunity” is to decipher fundamental sialoglycan functions at organismal, cellular, and molecular levels. The central concept of this Research Unit is to combine analysis of developmental and immunological aspects of sialobiology in order to gain insight into their intricate interplay. Because of their complexity, glycans have often been overlooked, but it became evident that they play critical roles in numerous biological and disease processes. We will focus on glycans that are capped by sialic acids, an abundant glycan class characterized by a huge structural diversity. Sialic acids are key components in many cellular communication processes and serve as critical determinant for the recognition of self. Thus, changes in the sialylation pattern translate into alterations with potential aberrancies in self-recognition, tissue homeostasis and immunological tolerance. Due to the structural complexity of sialoglycans and their central role in both developmental and immunological processes, interdisciplinary approaches are mandatory for a full understanding of the essential role of sialoglycans. Therefore, the Research Unit combines complementary expertise from developmental biology, immunology, neurobiology, structural biology, biochemistry, and stem cell glycomics to efficiently tackle key questions of sialobiology. A unique set of sialoglycan-specific mouse models, glyco-tools, and cutting-edge analytical methodologies will allow us to uncover how the multi-layered complexity of the sialome translates into biological functions. Our strategy will foster and exploit integrated approaches to catalyze advances in our understanding of processes at the crossroad of development and immunity such as induction and maintenance of immunological tolerance (e.g. at the fetal-maternal interface), immune cell development, and long-term maintenance of tissue homeostasis. Key objectives for the second funding period are: (i) Unravelling novel sialic acid functions in embryonic development, (ii) Understanding the role of sialoglycans in lymphocyte development and function, (iii) Dissecting the role of polysialic acid in preventing autoimmunity, (iv) Exploring structure and function of polysialic acid-recognizing immune receptors, (v) Understanding polysialic acid-chemokine interactions and their biological functions, (vi) Determining the functional role of sialic acid O-acetylation. We expect that our research program will provide novel insight into sialoglycan functions that will help to better understand the impact of glycans in the development of pregnancy complications as well as autoimmune and age-related inflammatory diseases.