Protein Quality Control
Head: Dr. Christian Münch
Mitochondria are essential for most cellular processes and a cell’s very own survival. To remain active and functional, mitochondria need to control the synthesis and folding of their proteins. However, many cellular perturbations, including major diseases like neurodegenerative diseases and cancer, can harm mitochondria’s protein folding homeostasis, with potentially fatal consequences for cells.
|Research in the Münch laboratory focuses on the mitochondrial protein quality control responses in mammalian cells upon mitochondrial protein misfolding, particularly the mitochondrial unfolded protein response (UPRmt). During protein folding stress in mitochondria, UPRmt elicits a transcriptional response to induce genes such as chaperonins to increase the mitochondrial folding capacity. Additionally, as we recently showed, UPRmt also contains a translational response that reduces the folding load of proteins inside mitochondria by reversibly halting mitochondrial translation (Figure). We aim to further understand and define the processes involved in the UPRmt and other mitochondrial stress responses upon protein misfolding and to gain insight into the pathways that protect from mitochondrial and cellular damage. The lab heavily relies on our expertise in quantitative mass spectrometry in combination with cutting-edge cell biological, biochemical, gene editing, and next-generation sequencing approaches as tools to address our biological questions.
We are grateful to the funders of our work: European Research Council (ERC Starting Grant), German Research Foundation and the Emmy Noether Program, HMWK LOEWE Center for Cell and Gene Therapy, CRC 1177 on Selective Autophagy (SFB), Johanna Quandt Young Academy at Goethe, Frankfurt Cancer Institute, Mildred-Scheel-Nachwuchszentrums Frankfurt, and Else Kröner-Forschungskolleg Frankfurt.
Dr. Christian Münch
Christian Münch studied Biochemistry at the University of Tübingen and the Max Planck Institutes in Martinsried and Tübingen. He obtained his PhD from the University of Cambridge (UK) where he performed his thesis work in Anne Bertolotti’s laboratory at the Laboratory of Molecular Biology (Cambridge, UK). His graduate work focused on the folding and prion-like properties of mutant SOD1 in the context amyotrophic lateral sclerosis, and earned him the prestigious British Neuroscience Association Postgraduate Award. After his graduation, Christian joined the laboratory of Wade Harper at the Harvard Medical School with an EMBO long-term fellowship to study protein quality control in mitochondria, particularly the mitochondrial unfolded protein response. Christian started as an independent group leader at the Institute of Biochemistry II in December 2016. His main research interests focus on mitochondrial quality control, in particular in determining the processes involved in the mitochondrial unfolded protein response and its role in human diseases.
Iris studied medicine at the University of Freiburg (Germany) and the University of Coimbra (Portugal). Focusing on the differentiation of human neural stem cells, she conducted her MD thesis work in the lab of Hans-Dieter Hofmann at the Department of Neuroanatomy. In 2014, she started her medical specialization in neurology at the University hospital Frankfurt and joined the neurooncology research group of Prof. Joachim Steinbach. Funded by the Frankfurt Research Funding and the Else Kröner-Kolleg, she started a joint project with the Münch lab in July 2018. In particular, her project focuses on autophagy and mitophagy as mechanisms of therapy resistance in glioblastoma cells.
Melinda studied biology with a focus on genetics and biochemistry at the Justus-Liebig-University in Giessen and received her Master’s degree in 2017. During her Bachelor’s and Master’s thesis work at the Institute of Biochemistry, she was involved in the analysis of the DNA mismatch repair system and the development of a novel circRNA-based therapeutic tool for HCV infection, respectively. In the beginning of 2018 she joined Christian Münch’s research group as a PhD student and is analyzing the mitochondrial unfolded protein response.
Ines studied Biochemistry at the University of Jena. For her diploma thesis she joined the Division of Viral Transformation Mechanisms of Prof. Rösl at the German Cancer Research Center in Heidelberg investigating the influence of human pappiloma virus on innate immune responses. Afterwards Ines joined the Protein Reaction Control group of Prof. Grininger at the Goethe University of Frankfurt. She worked on the expression and engineering of flavoproteins and polyketide synthases. In 2018 Ines started as a PhD student in the Protein Quality Control group of Dr. Münch analysing the signaling in the mitochondrial unfolded protein response.
After receiving his bachelor’s degree in pharmaceutical science in Egypt, Shady studied clinical pharmacy and became a Board Certified Pharmacotherapy Specialist. In 2017, he earned his master’s degree in Biochemistry from Uppsala University, Sweden. He conducted his master’s thesis in the Ludwig Cancer Institute, Uppsala university, in Johan Lennartsson’s lab under supervision of Professor Carl Henrik Heldin, chairman of the Nobel Foundation. His master’s thesis was about regulation of internalization, stability and signaling of platelet-derived growth factor receptor-β (PDFRβ) by ubiquitin specific protease 17 (USP17). In April 2018, he joined Christian Münch’s lab for his PhD to investigate the protein quality control in mitochondria, analyze the unfolded protein response in the mitochondria (UPRmt) and determine its signaling pathways.
Kevin studied biosciences at the Goethe-Universität in Frankfurt and received his bachelor´s degree in 2014. Afterwards he focused on molecular and cellular biology at the university of Heidelberg. During his master thesis in the Bukau lab in Heidelberg he worked on co-translational processes in the cell, using mainly ribosome profiling approaches together with Next-Generation sequencing. He received his Master in 2016 and is currently working as a PhD student in the lab of Christian Münch on the mitochondrial unfolded protein response.
Jonas was born in Frankfurt Main and studied biochemistry at the Goethe University Frankfurt. For his diploma thesis he joined the laboratory of Prof. Robert Ernst at the Buchmann Institute for Molecular Life Sciences and investigated the molecular mechanism of the yeast lipid saturation sensor Mga2. In a following project his focus went to the human lipid saturation machinery and possible regulators, utilizing in vitro and humanized-yeast based approaches. In January 2017, he then started his PhD in the Münch group analyzing the interplay of the mitochondrial unfolded protein response and mitochondrial quality control.
Dr. Georg Tascher
Georg studied human and molecular biology and did his PhD at the biochemical engineering institute (Prof. Elmar Heinzle), at Saarland university. During his thesis, he worked on organotypic cultures of hepatocytes for in vitro toxicology and implemented a LC-MALDI platform for the analysis of their secreted proteins. He then moved to Alain van Dorsselaer´s lab at CNRS Strasbourg working as a postdoc in the field of mass spectrometry-based quantitative proteomics within national and european projects. Georg joined the Mass Spectrometry Unit at the IBC2 in September 2017 and is responsible for method development, sample preparation, and maintenance of the mass spectrometry platform.
Dr. FX Reymond Sutandy
Dr. FX Reymond Sutandy Reymond was trained as a Biologist and obtained his Bachelor’s degree from Bandung Institute of Technology, Indonesia. He then moved to Taiwan to pursue his Master’s degree at the National Central University. Afterwards, he joined the laboratory of Julian König at the Institute of Molecular Biology (Mainz, Germany) to carry out his postgraduate work. During his PhD, Reymond developed a high-throughput technique to map trancriptome-wide binding sites of RNA binding protein called in vitro iCLIP. Using this technique, he studied the binding regulation of an important splicing factor, U2AF65. Reymond decided to expand his expertise in cell biology and joined Christian Münch’s laboratory in 2019 as a postdoctoral researcher to investigate the mammalian mitochondrial unfolded protein response, in particular its interconnection with apoptosis.
Aneesha studied Biology at Imperial College London (UK) with a focus on immunology and neuroscience. As part of her degree, she did a ‘Year in Research’ at Lancaster University in the lab of Prof. David Allsop. Her project focussed on the redox properties of misfolded protein aggregates of amylin and amyloid-β. She is now completing her masters in Interdisciplinary Neuroscience at Goethe-Universität, Frankfurt. As part of her master thesis, she is working in the laboratories of Dr. Christian Münch and Prof. Georg Auburger, using quantitative proteomics to understand the role of RNF213 in the neurological disorder Moyamoya disease.
Süleyman completed his undergraduate in molecular biology and genetics at Izmir Institute of Technology in Turkey. During his Master's at Acıbadem Mehmet Ali Aydınlar University, he worked on CDP-choline's effects on mitophagy and mitochondrial dynamics. He also carried out work on TFEB in Katja Simon’s Lab at the University of Oxford. He joined the Münch lab in 2019 to study the effects of mitochondrial stress on mitochondrial proteostasis and mitophagy.
Sebastian studied medicine at the University of Regensburg (Germany). He conducted his MD thesis work in the lab of Prof. Dr. Ernst Tamm at the Department of Anatomy and Embryology. In 2016, he started his medical residency in internal medicine with a specialization in Hematology & Oncology at the University Hospital Frankfurt and joined the acute myeloid leukemia research group of Prof. Dr. Christian Brandts. With funding by the Mildred-Scheel-Nachwuchszentrum Frankfurt, he started a research project with the Münch lab in 2019, using quantitative proteomics to understand protein dynamics in acute myeloid leukemia.
In 2012, Martin graduated as Biological Technical Assistant (BTA) in Koblenz and started working in the Kerschensteiner laboratory at the Institute of Clinical Neuroimmunology in Munich focusing on protein production for the MS research. From 2016 till 2019, he was part of the research group Schmidt at the Institute for Microscopic Anatomy and Neurobiology in Mainz, gaining further experience in the production and purification of proteins for cancer research. In 2020, Martin joined the IBCII to support the Protein Quality Control Group of Christian Münch and the Quantitative Mass Spectrometry Unit.
After completing an apprenticeship as biological lab technician, Jasmin studied Biochemistry at Goethe University in Frankfurt am Main. She found her passion for cellular stress responses during a three-month internship in Peter Walter’s lab at University of California, San Francisco. Jasmin obtained her PhD from Heidelberg University, where she joined the laboratory of Sebastian Schuck at the Center for Molecular Biology of Heidelberg University (ZMBH). During her thesis work, she investigated a stress-induced microautophagic pathway for selective degradation of endoplasmic reticulum and demonstrated the involvement of the ESCRT machinery. Jasmin joined the Münch lab in the beginning of 2020 as a postdoctoral researcher to study the mitochondrial unfolded protein response.
SARS-CoV-2 infected host cell proteomics reveal potential therapy targets
The new coronavirus – SARS-CoV-2 – has been quickly spreading around the globe since the beginning of 2020. The resulting disease COVID-19 has become a pandemic with over 100,000 infected people in over 100 countries and leading to thousands of deaths. We teamed up with Jindrich Cinatl at the Institute of Medical Virology (University Hospital Frankfurt) to study SARS-CoV-2 and identify new therapy options. We developed a novel cellular infection system with viral isolates from a COVID-19 patient, characterized by proteomics how the host cell changes over time after SARS-CoV-2 infection, and tested drugs targeting the identified pathways. We revealed a number of drugs that efficiently prevented virus replication in cells showing potential therapeutic strategies against COVID-19.
Head: Dr. Christian Münch
Institute of Biochemistry II
University Hospital Frankfurt
Theodor-Stern-Kai 7 / Building 75
60590 Frankfurt am Main
Tel: +49 (0) 69 6301 6599
Fax: +49 (0) 69 6301 5577
PROteostasis Group of European New InvEstigators (PROGENIE)
Proteins underlie numerous processes ranging from synthesis, folding, modification, trafficking, to degradation. The correct interplay of these affects is require for proteins to carry out their proper functions in cells. The overall process to keep all these functions in balance is called protein homeostasis (proteostasis). The proteostasis field includes aspects such as chaperones, the ubiquitin-proteasome system, autophagy, and stress responses. In the last years, proteostasis has become of particular interest due its key role in ageing and pathologies ranging from neurodegeneration to cancer.
A couple of years ago, it became apparent that there is a lack of opportunity for new group leaders to discuss general topics specific to this career stage and to have a forum to discuss their recent results with an opportunity to gain advice from experts from the different areas of proteostasis. The result was the formation of the PROGENIE network (PROteostasis Group of European New InvEstigators). The group came to life with our first meeting of 13 young investigators in November 2017. This first group was largely recruited from the protein folding community and since has been gradually growing in size and scientific focus, now covering a wider part of proteostasis.
Our main activity is a yearly PROGENIE meeting organized by and for PROGENIE members only. There, everybody has a chance to present their research and to gain feedback (ranging from experimental suggestions to publication strategies), exposure, and to develop collaborations. In additions, we address topics important for new investigators regarding the field, science structures, grant opportunities, and strategies and advise for topics involved in setting up and running a laboratory. Resulting from these discussions, PROGENIE members published guidelines for early-career group leaders (doi:10.15252/embr.201847163).
In addition, it became clear that there is a need for training opportunities for graduate students and postdocs in the ever-growing proteostasis field. As a result, we initiated a biannual ‘Autumn School on Proteostasis’ with leaders in the proteostasis field and PROGENIE members offering presentations on review-like overviews on different aspects of proteostasis, conference-type updates on current research, and career advice. The schools offers opportunity to attendees to present their research projects and to meet leaders in the field and get their advice and input. We ran the first school in November 2018 in Croatia, which was a great success with a good atmosphere to network and to learn about proteostasis and science in general. Nicely, it resulted in four attending postdocs to write a review about the school. The second proteostasis school will take place November 2020 in Israel, funded by EMBO/FEBS. In her memory, we named the series ‘Susan Lindquist School on Proteostasis’.
Become a member
We are looking for new investigators located in Europe with a visible track record in the proteostasis field and who are in the beginning of setting up their own laboratories. If you are interested in joining, please send an email to with a short paragraph about you and your research.
Claes Andréasson (Stockholm University, Sweden)
Ivana Bjedov (University College London, UK)
Marion Bouchecareilh (University of Bordeaux, CNRS, INSERM, France)
Piotr Bragoszewski (University of Warsaw, Poland)
Matthias Feige (Technical University of Munich, Germany)
Olivier Genest (Aix Marseille University, CNRS, France)
Paolo Grumati (Telethon Institute of Genetics and Medicine, Italy)
Elif Karagoez (Max Perutz Laboratories and University of Vienna, Austria)
Anton Khmelinskii (Institute of Molecular Biology at Mainz, Germany)
Janine Kirstein (University of Bremen, Germany)
Anita Krisko (University Medical Center, Göttingen, Germany)
Christian Münch (Goethe University Frankfurt, Germany)
Natalia Rodríguez-Muela (DZNE-Dresden, Germany)
Rina Rosenzweig (Weizmann Institute of Science, Israel)
Adrien Rousseau (MRC-PPU, UK)
Juha Saarikangas (University of Helsinki, Finland)
Ritwick Sawarkar (MRC and University of Cambridge, UK)
Ruth Scherz-Shouval (Weizmann Institute of Science, Israel)
Reut Shalgi (Technion, Israel)
Rebecca Taylor (MRC-LMB, UK)
Patricija Van Oosten-Hawle (University of Leeds, UK)