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
New ubiquitin chemistry regulates life processes
1st December 2016
In the latest issue of Cell, a team around IBC2 director and SFB 1177 speaker Ivan Dikic reveals molecular details of a novel ubiquitination mechanism that may affect numerous life processes. Earlier this year, U.S. colleagues reported that Legionella enzyme SdeA is capable of catalysing ubiquitination single-handedly. Now, the Frankfurt scientists together with collaborators from the MPI for Biology of Ageing (Cologne) have elucidated the chemistry behind and discovered a hitherto unknown type of linkage between ubiquitin and target proteins. Unlike the conventional ubiquitination reaction, the novel one is NAD-dependent, involving an ADP-ribose intermediate and resulting in the attachment of ubiquitin to substrate serine residues via a phosphodiester bond.
While those findings alone are breaking new ground, the discovery went even further: The team showed that the Legionella enzyme does not only transfer ubiquitin onto target proteins, but also leaves behind a complete pool of chemically modified, phosphoribosylated ubiquitin. Phosphoribosylated ubiquitin almost completely inhibits the conventional ubiquitination system and thereby affects essential cellular processes, e.g. proteasomal protein degradation, mitophagy and pro-inflammatory signalling. This explains the pathogenic effects of Legionella infection in immunocompromised patients, who often suffer from extensive lung tissue damage despite antibiotic treatment. The insight generated by the Dikic team may now open the road to the development of new antibacterial agents, which could complement conventional antibiotics by limiting the cellular damage induced by bacterial enzymes.
Link to Cell paper.
Link to German press release.
Link to English press release.
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International marketing concept of UBAUT networks receives DFG award
1st December 2016
As the German Research Foundation (DFG) announced today, Goethe University (GU) is one of the winners of the 2016 Competition for International Research Marketing Ideas.
The awarded concept “Let’s talk about UBAUT” was initiated by SFB 1177 on Autophagy (http://www.sfb1177.de), LOEWE Ub-Net (LINK TO http://www.proloewe.de/ubnet) and IBC2, and in collaboration with GU’s Departments for Internationalization and Marketing and Communication.
The prize is awarded with 100,000 €, enabling the ubiquitin and autophagy networks now to implement a wide range of marketing measures for increasing their international visibility and attract highly qualified international colleagues to the Rhine Main biomedical research area. The program follows a ‘bottom-up’ approach which will be driven by LOEWE Ub-Net and SFB 1177 scientists. It comprises ambassador visits to renowned research institutions in the US as well as short stipends for international scientists wishing to pursue a career in Germany and a strategy outreach meeting.
Link to DFG press release.
Link to GU press release.
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Nobel Prize in Physiology or Medicine 2016 for autophagy researcher: Congratulations to Yoshinori Ohsumi
3rd October 2016
The Nobel Assembly at Karolinska Institutet decided today that the 2016 Prize is awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy. The Japanese scientist is considered as the founding father of autophagy research: He identified the first autophagy genes in yeast, elucidated the underlying mechanisms and showed that a similar sophisticated machinery exists in human cells. Ohsumi holds a professorship at the Tokyo Institute of Technology in Japan. He is the only Laureate receiving the prize this year, underlining the significance and breakthrough character of his discoveries. The announcement came as fantastic news for the entire field of autophagy research, and the SFB 1177 consortium sends sincerest congratulations to Yoshinori Ohsumi.
Link to the Nobel Academy Press Release
Link to ZDF heute journal report including statement from SFB 1177 member Simone Fulda