SFB 1403:  Cell Death in Immunity, Inflammation and Disease

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.

DFG Programme Collaborative Research Centres

• A01 - Mechanisms of cell death-induced inflammation (Project Head Pasparakis, Manolis )
• A02 - Cross-talk between dying and bystander cells in vitro and in vivo: an optogenetics approach (Project Heads Garcia Sáez, Ana Jesús ;  Pasparakis, Manolis )
• A03 - The role of metalloprotease activity in necroptosis driven inflammation (Project Head Hornung, Veit )
• A04 - Molecular pathways of gasdermin pore formation and repair (Project Heads Latz, Eicke ;  Schmidt, Florian Ingo )
• A05 - Inflammatory signalling in ferroptotic cell death (Project Head von Karstedt, Silvia )
• A06 - The role of mitochondria for cellular protection against ferroptosis (Project Head Langer, Thomas )
• A07 - Control of macrophage cell death in skin homeostasis and repair (Project Head Eming, Sabine )
• A09 - Regulated cell death and kidney fibrosis as a consequence of mutation of cilia-associated genes (Project Heads Benzing, Thomas ;  Schermer, Bernhard )
• A10 - Cell death and inflammation modulated by the ubiquitin E3 ligase activities within LUBAC in metabolic inflammation (Project Heads Peltzer, Ph.D., Maria de las Nieves ;  Walczak, Ph.D., Henning )
• A11 - NLRP10 inflammasome mediated anti-inflammatory cell death (Project Head Latz, Eicke )
• A12 - The role of a previously unrecognised E3 ligase in regulating TLR3 signalling (Project Head Walczak, Ph.D., Henning )
• A13 - Contribution of microglia cell death to tau pathology in Alzheimer’s disease and other tauopathies (Project Head Ising, Christina )
• A14 - Immunological dissection of cell death-induced inflammation in human disease (Project Head Oda, Ph.D., Hirotsugu )
• B01 - Role of apoptotic caspases in macrophage-mediated anti-bacterial immunity (Project Heads Fritsch, Melanie ;  Kashkar, Hamid )
• B02 - Cell death signalling peptides in maize immunity – Molecular mechanisms of signal generation, transduction and perception (Project Heads Döhlemann, Gunther ;  Huesgen, Pitter ;  Misas Villamil, Johana )
• B03 - Cell death regulation and function in plant-fungal symbiosis (Project Head Zuccaro, Alga )
• B05 - Mechanisms and consequences of inflammasome mediated mitochondrial impairment in Mycobacterium tuberculosis infected myeloid cells (Project Head Rybniker, Ph.D., Jan )
• B06 - The evolution of regulated necrotic cell death (Project Head Hofmann, Kay )
• B07 - Ultra-structure of the plasma membrane harbouring MLKL oligomers and MLKL-mediated Ca2+ influx during plant and animal immunogenic cell death (Project Heads Chai, Jijie ;  Garcia Sáez, Ana Jesús ;  Maekawa, Ph.D., Takaki )
• B08 - Connecting plant sensor NLRs to host cell death responses (Project Heads Chai, Jijie ;  Parker, Jane E. ;  Schulze-Lefert, Paul )
• B09 - Immune-related cell death pathways as targets of fungal virulence strategies (Project Head Saur, Ph.D., Isabel Marie-Luise )
• CP01 - Central Tasks (Project Head Pasparakis, Manolis )
• CP02 - Genetically engineered mouse models for the study of cell death and its role in immunity and inflammation (Project Head Pasparakis, Manolis )
• CP03 - Cell Death Assessment Unit (Project Heads Fritsch, Melanie ;  von Karstedt, Silvia ;  Kashkar, Hamid )
• CP04 - Proteomic dissection of cell death-mediated protein release and proteolysis (Project Heads Huesgen, Pitter ;  Meissner, Felix )
• INF - Research data management, analysis and bioinformatics support (Project Heads Hofmann, Kay ;  von Karstedt, Silvia ;  Wesner, Stefan )
• MGK - Integrated Research Training Group (“Cell-Death-RTG”) (Project Heads Misas Villamil, Johana ;  Rybniker, Ph.D., Jan ;  Schermer, Bernhard ;  Zuccaro, Alga )

• A08 - Ferroptosis and regulated cell death in sulphite oxidase deficiency (Project Head Schwarz, Günter )

Applicant Institution Universität zu Köln

Participating University Ludwig-Maximilians-Universität München; Rheinische Friedrich-Wilhelms-Universität Bonn

Participating Institution Deutsches Rheuma-Forschungszentrum Berlin (DRFZ); Max-Planck-Institut für Biologie des Alterns; Max-Planck-Institut für Pflanzenzüchtungsforschung

Spokesperson Professor Dr. Manolis Pasparakis