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
26. Apr 2022
CRC 1177 speaker Ivan Đikić and CRC1177 member Martin Beck have been awarded with an Advanced Grant of the European Research Council (ERC). This is the third time Ivan Đikić receives the prestigious grant that comes along with research funding in the amount of € 2.5 million for the next five years. Martin Beck has previously been awarded with both an ERC Starting and an ERC Consolidator Grant.
With his grant, Ivan Đikić intends to unravel molecular mechanisms of endoplasmic reticulum (ER) remodelling via ER-phagy pathways. As the largest intracellular membrane system, the ER covers important functions in numerous processes. To fulfill its diverse tasks, the ER is constantly adapting its shape. Within his project, Ivan Đikić will now explore the novel concept of ubiquitin-driven receptor clustering igniting the entire process of membrane remodeling. The emerging data will not only provide new insights in the organelle dynamics, but will also help to understand the impact of ER and ER-phagy on neurodegenerative diseases, cancer and infections, which has been known to exist for a long time. The ERC project builds on a decade-long success story of continuous funding in the field – especially on results generated within the CRC 1177, but also on the HMWK-funded large-scale project on ubiquitin networks (Ub-Net), which ran until 2017 and was also led by Ivan Đikić.
In his project, Martin Beck plans to tackle the hypothesis that nuclear pores may act as self-regulating valves for flux across the nuclear envelope. Nucelar pore complexes are known to enable transport of macromolecules between the cytoplasm and the nucleus. Recent findings indicate that there may be more function beyond nucleocytoplasmic transport. The results of this research will contribute to a better understanding of how cells deal with acute mechanical stress and reveal new therapeutic options for diseases.
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18. Aug 2021
Christian Münch, group leader at the IBC2, will receive the Otto Meyerhof Award 2021 by the German Society for Biochemistry and Molecular Biology (GBM). The award honours the outstanding research performance of young investigators under 40. The research of the Münch group focuses on the elucidation of cellular stress responses upon protein misfolding and as a consequence of disease-causing mutations and infections, building on Münch’s in-depth expertise in quantitative mass spectrometry and system biology approaches.
To quantitatively measure small changes in protein translation, the group developed a new analytical method called multiplexed enhanced protein dynamics (mePROD) proteomics. This approach has helped to study the effects of mTOR inhibition and integrated stress response activation (Klann et al., Mol Cell 2020). It is broadly adaptable to very different research questions, as very successfully shown by Münch and his team after onset of the corona pandemic: Within a matter of a few weeks, they were able to determine host cell responses to SARS-CoV-2 infection (Bojkova et al., Nature 2020) providing important insights into changes imposed by the virus upon host cells. Further analyses revealed cellular pathways that are crucial for SARS-CoV-2 replication in cells (Klann et al., Mol Cell 2020) These studies pointed to new therapeutic targets that are now under clinical evaluation or approved for the treatment of COVID-19 patients.
The Otto Meyerhof Award is endowed with 5,000 Euros, funded by Boehringer Ingelheim Pharma. The prize ceremony will take place virtually on the 16th of September, with Christian Münch presenting the award lecture on „Dynamic protein synthesis changes in stress and disease”. For those wishing to attend the event, registration until the 14th of September is required: https://gbm-online.de/gbm-awards-event.html.
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07. Jun 2021
Starting in July 2021, Professor Dr. Liliana Schaefer will take over the new Editor-in-Chief of the American Journal of Physiology-Cell Physiology.
Dr. Schaefer is an expert in Matrix biology, Pharmacology and Nephropharmacology and has contributed significantly to the field of Physiology by unraveling that two components of the extracellular matrix, decorin and biglycan, act as endogenous “danger” signals when in soluble form in the blood and body fluids.
She is a Professor of Pharmacology at the Institute of Pharmacology and Toxicology, Goethe University in Frankfurt, Germany and Adjunct Research Professor of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, USA. In addition, Liliana Schaefer has been PI of SFB 1177 since the first funding period in 2016 and is currently represented with her E02-project “Selective autophagy network in diabetic nephropathy”.
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