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FAN - Frankfurt Autophagy Network
The Frankfurt Autophagy Network is a research consortium established in 2011 coordinated by Prof. Dr. Ivan Dikic and Prof. Dr. Simone Fulda. Principal Investigators of Johann Wolfgang Goethe University Frankfurt and Johannes Gutenberg University Mainz have created an efficient and stimulating research environment with close cooperations between clinical and basic research.
Autophagy is an ancient intracellular self-defense pathway that allows cells, tissues and organs to survive various onslaughts such as nutrient deprivation, inflammation, hypoxia and numerous other stresses. Mechanistically, autophagy is the catabolic process of delivering cytosolic cargo, such as protein aggregates and organelles, to the lysosome for degradation. This form of ‘garbage removal’ starts with the formation of an isolation membrane, the origin of which has been reported to be the ER, Golgi and the mitochondria. The double membrane structure then encapsulates, seals and eventually fuses with the lysosome where the cargo is broken down into its constituent components and recycled to fuel the growth and proliferation of the cell. Cells thereby prevent the toxic accumulation of damaged or unnecessary components and maintain metabolic homoeostasis. Autophagy is upregulated when cells require intracellular nutrients and energy such as during starvation, growth factor withdrawal or in the context of high bioenergetic demands.
This process is highly conserved from yeast to mammals and is essential for proper development of the organism. This is exemplified by the genetic knockout of either Atg5 or Atg7 in mice, leading to neonatal lethality, and knockout of Beclin1 (mammalian Atg6), which is early embryonic lethal. The number of autophagy (Atg) proteins is staggering. The current total in yeast (Saccharomyces cerevisiae) is 33 Atg proteins and counting, all of which regulate various aspects of the isolation membrane initiation, elongation, closure and fusion events. The core component proteins that regulate autophagy have been intensively studied. However, less is known about the inputs that can specifically alter recruitment of these components, post-translational modifications that influence autophagy flux and how autophagy controls physiological and pathophysiogical processes in the organism. Since autophagy is involved in the pathogenesis of various human diseases, including e.g. cancer, neurodegenerative diseases or aging, a better understanding of autophagy regulation under normal conditions and in diseases opens new perspectives for the development of novel diagnostic and therapeutic strategies.
Main scientific objectives are:
• To analyze structural, molecular and functional aspects of autophagy networks
• To determine the role of autophagy in human diseases and evaluate the possibility for therapeutically targeting the autophagy processes
Participating Persons and Instituts:
• Goethe University Hospital: Dr. Christian Behrends, PD Dr. Christian Brandts, Prof. Dr. Ivan Dikic, Dr. David McEwan, Prof. Dr. Simone Fulda, PD Dr. Donat. Koegel, Prof. Dr. Michel Mittelbronn, Prof. Dr. Hubert Serve, Prof. Dr. Irmgard Tegeder.
• Goethe University, Biophysical Chemistry: Prof. Dr. Volker Dötsch
• Goethe University, Molecular Developmental Biology: Prof. Dr. Heinz D. Osiewacz
• Gutenberg University, Pathobiochemistry: Prof. Dr. Christian Behl
• Frankfurt Institute for Molecualar Life Sciences (FMLS): Prof. Dr. Andreas Reichert, Prof. Dr. Ernst Stelzer, Dr. Martin Vabulas, Dr. Francesco Pampaloni
• Center for Membrane Proteomics (CMP): Dr. Mika Ruonala
For more information please contact Ivan Dikic or Julia Sommer (administrator).
