Molecular and Functional Characterization of Selective Autophagy
Autophagy is a highly conserved catabolic process that serves as a quality control mechanism in cells by selectively removing damaged and superfluous organelles or other harmful cytosolic material, such as aggregated proteins or invaded bacteria. Under stress or energy restriction autophagy provides recycled building blocks for the synthesis of new cellular components. Three different types of autophagy can be distinguished: macroautophagy, microautophagy and chaperone-mediated autophagy. This SFB focuses on macroautophagy (hereafter referred to as autophagy), a multi-step cellular process by which cytosolic material is engulfed by a double-membrane, termed autophagosome after closure, which eventually fuses with a lysosome in order to eliminate its content. Autophagy plays a vital role in protecting against disease, but in recent years it became clear that the effect of autophagy is highly contextual. While it acts for instance as an anti-tumorigenic mechanism in healthy cells, cancer cells exploit the cytoprotective effect of autophagy to overcome stress conditions and nutrient limitation caused by rapid tumor growth. SFB 1177 aims at gaining a more detailed insight into the mechanistic details of autophagic pathways to better understand its role in disease development and eventually exploit this knowledge therapeutically.
Funded by DFG
13. May 2020
Despite COVID-19 quickly developing to a world-wide pandemic, treatment options remain limited. The mechanisms by which SARS-CoV-2 enters cells, how the cell responds to infection, and which therapeutic approaches could stop viral replication remain unclear. In a manuscript published today in the renowned journal Nature, IBC2 group leader Christian Münch, together with Jindrich Cinatl (Institute of Medical Virology, University Hospital Frankfurt), provide with answers to these questions. Using SARS-CoV-2 isolated from COVID-19 patients in Frankfurt, they established a cellular model to study coronavirus infection. Using a recently developed novel translation proteomics method (https://doi.org/10.1016/j.molcel.2019.11.010), they analysed how viral infection changes cellular protein synthesis and abundance. This revealed several cellular pathways strongly modulated upon SARS-CoV-2 infection. Strikingly, using drugs targeting these pathways – some of which are approved for use in other diseases – prevented SARS-CoV-2 replication in cells. This reveals potential new therapeutic strategies for specific COVID-19 treatments and have been picked up for ongoing (ribavirin) and planned (2-deoxy-glucose) clinical trials.
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25. Nov 2019
We are very happy to announce that the German Research Foundation (DFG) will fund this SFB for another four years with >12 M €. This enables us to continue the ambitious and highly integrative work program to better understand the mechanistic regulation of autophagy networks in health and disease. With most projects critically depending on state-of-the-art technologies, a key part of the 2nd funding proposal relates to the substantial expansion of the central platforms. Besides extending the existing quantitative proteomics unit to include modeling and simulation methods, the consortium will also establish new platforms for genomic and chemical screening and for quantitative phenotype analysis. To close the gap on missing expertise, the team was also significantly enlarged, and we welcome all new colleagues from the Universities of Mainz, Tübingen and Freiburg and the Max Planck Institute of Biophysics on board!
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Initiated by SFB 1177 Vice Speaker Christian Behl
24. Oct 2019
A small group of experts and early-career researches met in New York to exchange latest results and views on „Alzheimer’s, Related Disorders and Autophagy“. So far, researchers worldwide have not been successful to unravel the mechanisms underlying neurodegenerative diseases. More recently, malfunctioning autophagy-related processes have been discussed as a possible cause. On this occasion, among others, SFB 1177 Speaker Ivan Dikic and Vice Speaker Christian Behl presented their latest data to the audience. The scientific workshop was followed by an evening session with more general discussions on future perspectives of Alzheimer’s treatment.
The event was organized by Christian Behl (University Medical Center of the Johannes Gutenberg University Mainz) and Ralph Nixon (Nathan S. Kline Institute for Psychiatry, NYU Langone Medical Center) in cooperation with the German Center for Research and Innovation (DWIH, New York). It was funded by the Dr. Eberhard Strebel-Stiftung and the University Medical Center of the Johannes Gutenberg University in Mainz.
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