SFB 1177:  Molecular and Functional Characterization of Selective Autophagy

• Subject Area: Biology ; Medicine
• Term: since 2016
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259130777

Selective autophagy is an intracellular catabolic process targeting various cellular components for lysosomal degradation. It is essential for cellular homeostasis and any deregulation contributes to pathophysiology of human diseases like cancer, neurodegeneration, and infections. This CRC has been the first concerted, interdisciplinary effort in the field of autophagy in Germany, and, as such, has gained international visibility. In the past seven years, we have generated detailed insights into the molecular basis of autophagy and its regulation, into functions of individual selective autophagy pathways, and the role of autophagy in human diseases. Additionally, we have contributed to advancing the field technologically, and today Frankfurt is recognized as an important technology hub for autophagy research in Germany. For the 3rd funding period, we propose bringing our research to high integrative and interdisciplinary levels by creating teams of multidisciplinary researchers that address several challenging questions in autophagy. Major areas of interest include lipid and membrane remodeling, dynamics of organelle turnover, the role of autophagy in neurodegeneration, in immunity, and inflammation. Autophagosome biogenesis is one of the longstanding conundrums in the field, and we will study how cargo properties, distinct phospholipids, and proteins influence it. With respect to aging and neurodegeneration, we aim to elucidate the molecular requirements for autophagic degradation of condensates, and further improve our understanding of the dynamic in vivo regulation of selective autophagy processes. We will also expand our efforts in dissecting the antibacterial functions of autophagy. In the field of immunity and inflammation, we will tackle several emerging topics: the crosstalk of selective autophagy and death signaling in inflammatory tissue damage, and the role of secretory autophagy in immune homeostasis. Finally, we will investigate the role of autophagy in hematopoiesis. We have completed several projects that formed a critical seed for translational networks Importantly, we have incorporated many new female and younger generation leaders in the 3rd funding period. We will restructure our service platforms to adapt to the changed needs of the consortium: Z01 platform will maintain its activities of quantitative proteomics and modeling of molecular dynamics, while Z02 platform will support the consortium with advanced imaging and phenotypic screening technologies. The highly successful education program of the CRC will be continued, encompassing both the Integrated Research and Training Group and widely visible events such as the Frankfurt Conference Series on Quality Control in Life Processes.

• DFG Programme: Collaborative Research Centres

Current projects

• F01 - Avidity-driven assembly and properties of cargo in selective autophagy (Project Heads Kraft, Claudine ;  Wilfling, Florian )
• F02 - Molecular principles guiding lipid structure and function of autophagosomes (Project Heads Bhaskara, Ph.D., Ramachandra M. ;  Kern, Andreas ;  Pohl, Christian )
• F03 - Regulation of aggrephagy by co-chaperones and assisting proteins (Project Heads Behl, Christian ;  Heilemann, Mike ;  Kaulich, Ph.D., Manuel )
• F04 - Control of aberrant TDP-43 phase transitions by the selective autophagy machinery (Project Heads Dormann, Dorothee ;  Hummer, Gerhard )
• F05 - Regulation of autophagy by microproteins and RNA modifications (Project Heads Dikic, Ivan ;  Kaiser, Stefanie )
• F06 - Regulatory mechanisms and dynamics of ER-phagy receptors clustering (Project Heads Heilemann, Mike ;  Stolz, Alexandra )
• F07 - Pexophagy and mitophagy in cellular homeostasis, aging and disease (Project Heads Bremm, Anja ;  Eimer, Stefan )
• F08 - Mitophagy during mitochondrial damage and cellular rejuvenation (Project Heads Bibli, Ph.D., Sofia Iris ;  Münch, Christian )
• F09 - Bacterial evasion of selective autophagy pathways (Project Heads Dikic, Ivan ;  Dötsch, Volker )
• F10 - Molecular analysis of physiological and BPAN-related WIPI4 functions (Project Heads Behrends, Ph.D., Christian ;  Proikas-Cezanne, Tassula )
• F11 - Interplay between autophagy and inflammatory cell death in organ fibrogenesis (Project Heads Kögel, Donat ;  Schaefer, Liliana )
• F12 - Autophagy mechanisms in intercellular sensing of tissue homeostasis by the immune system (Project Heads Herhaus, Lina ;  Weigert, Andreas )
• F13 - Autophagy in bone marrow adipocytes and its effect on healthy and malignant hematopoiesis and ageing (Project Heads Brandts, Christian ;  Krause, Daniela ;  Simon, Anna Katharina )
• MGK - Integrated Research Training Group (IRTG) (Project Heads Behl, Christian ;  Bremm, Anja ;  Dötsch, Volker ;  Pohl, Christian )
• Z - Central tasks of the CRC (Project Head Dikic, Ivan )
• Z01 - Quantitative proteomics and integrated systems biology (Project Heads Behrends, Ph.D., Christian ;  Beli, Petra ;  Bhaskara, Ph.D., Ramachandra M. ;  Dikic, Ivan ;  Hummer, Gerhard ;  Münch, Christian )
• Z02 - Imaging and phenotypical screening platform (Project Heads Eimer, Stefan ;  Heilemann, Mike ;  Pohl, Christian ;  Stolz, Alexandra ;  Wilfling, Florian )

Completed projects

• A04 - Regulatory interplay between autophagosomal and endosomal pathways (Project Head Dikic, Ivan )
• B02 - Autophagy in the cellular response to genotoxic stress (Project Head Beli, Petra )
• B05 - Protein engineering of sensors and modulators of autophagy (Project Head Ernst, Andreas )
• C03 - Crosstalk of autophagy and inflammatory signaling pathways during acute intestinal inflammation (Project Head Greten, Florian R. )
• D03 - Deubiquitinating enzymes in selective autophagy (Project Heads Beli, Petra ;  Bremm, Anja )
• D04 - Selective autophagy in proteostasis maintenance (Project Head Behrends, Ph.D., Christian )
• D05 - Molecular principles of ER-phagy pathways (Project Heads Dikic, Ivan ;  Hummer, Gerhard )
• D06 - Autophagy in ribosome biogenesis and quality control (Project Head Müller, Stefan )
• D07 - Selective autophagy of mitochondria and peroxisomes in organismic aging and development (Project Heads Eimer, Stefan ;  Osiewacz, Heinz Dieter )
• D09 - Structural characterization of domain-domain interactions in autophagy (Project Heads Dötsch, Volker ;  Knapp, Stefan )
• E01 - Serine ubiquitination and regulation of autophagy upon Legionella (Project Heads Dikic, Ivan ;  Heilemann, Mike )
• E05 - Exploring epithelial cell mitophagy as an inducer of adaptive immunity (Project Head Greten, Florian R. )
• E06 - Autophagy regulates drug response in activated B cell-like diffuse large B cell lymphoma (Project Heads Oellerich, Thomas ;  Serve, Hubert )
• E07 - Molecular mechanisms of WDR24-induced autophagy: Role in AML proliferation and survival (Project Head Serve, Hubert )
• E08 - Targeting selective autophagy in acute myeloid leukemia (Project Heads Brandts, Christian ;  Knapp, Stefan )
• E09 - Organelle-specific autophagy pathways in regulation of cell death (Project Heads Fulda, Simone ;  Kögel, Donat ;  van Wijk, Sjoerd )
• Z02 - Chemical and genomic screening (Project Heads Kaulich, Ph.D., Manuel ;  Stolz, Alexandra )

• Applicant Institution: Goethe-Universität Frankfurt am Main
• Participating University: Albert-Ludwigs-Universität Freiburg; Eberhard Karls Universität Tübingen; Johannes Gutenberg-Universität Mainz; Ludwig-Maximilians-Universität München
• Participating Institution: Georg-Speyer-Haus; Institut für Tumorbiologie und experimentelle Therapie; Max-Delbrück-Centrum für Molekulare Medizin (MDC); Max-Planck-Institut für Biophysik
• Spokesperson: Professor Dr. Ivan Dikic