FOR 2953:  Sialic Acid as Regulator in Development and Immunity

• Subject Area: Biology ; Medicine
• Term: since 2019
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409784463

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.

• DFG Programme: Research Units
• International Connection: Austria

Projects

• Coordination Funds (Applicant Mühlenhoff, Martina )
• DECIPHERING SIALIC ACID O-ACETYLATION (Applicant Mühlenhoff, Martina )
• Deciphering the Function and Regulation of the B Cell Intrinsic a2,6-Sialylation Network (Applicants Nimmerjahn, Falk ;  Werner, Anja )
• DISSECTING THE ROLE OF SIALOGLYCANS IN EMBRYONIC DEVELOPMENT (Applicant Weinhold, Birgit )
• DISSECTING THE ROLE OF SIALOGLYCANS IN EMBRYONIC DEVELOPMENT (Applicant Abeln, Markus )
• Expanding the glycoanalytical toolbox for understanding the role of glycans in pluripotent stem cell biology (Applicant Büttner, Falk )
• Neuroprotective role of the ‘sialic acid – SIGLEC’ axis in the central nervous system (Applicant Neumann, Harald )
• Novel functions of polysialic acid in kidney and immune cell development (Applicant Münster-Kühnel, Anja )
• Polysialic acid in Siglec- and chemokine-dependent responses of tumor-associated macrophages (Applicant Hildebrandt, Herbert )
• Structural Biology of Polysialic Acid Recognition (Applicants Stehle, Thilo ;  Zocher, Ph.D., Georg )
• The importance of sialoglycans for lymphocyte development and function (Applicant Nitschke, Lars )
• The role of polysialic acid in adaptive immunity and peripheral tolerance (Applicant Sixt, Michael )

• Spokesperson: Privatdozentin Dr. Martina Mühlenhoff