12th January 2020 – SARS-CoV-2 infection profile and therapeutic strategies.  Since the beginning of 2020, a new coronavirus (SARS-CoV-2) has been spreading, leading to a pandemic with > 126,000 infections around the globe recorded until today. In people, the virus causes a disease named COVID-19, which can cause severe respiratory failure and has already led to more than 4,600 deaths. 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. Now, IBC2 group leader Christian Münch, together with Jindrich Cinatl (Institute of Medical Virology, University Hospital Frankfurt), provides some 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, 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.

Link to preprint.
Link to lab website.
Link to online data tool.


Image frontpage: credits to Bojkova et al. and Arek Socha/Pixaby



21st February 2020 –Deubiquitinases (DUBs) are regulated by hydroxylation. DUBs are vital for the regulation of ubiquitin signals, and both their catalytic activity and their target selection needs to be tightly controlled. As reported in today’s issue of the Journal of Biological Chemistry, the group of Anja Bremm identified asparagine hydroxylation as a novel post-translational modification involved in the regulation of the DUB Cezanne. Cezanne controls essential cellular functions and signaling pathways. The team demonstrated for the first time that the predicted ubiquitin-binding domain (UBD) in Cezanne is functionally active and interacts with ubiquitin in a unique manner. At the same time, they discovered a novel regulatory mechanism: Hydroxylation within this domain inhibits ubiquitin binding and therefore may affect Cezanne’s ability to bind specific target proteins via its UBD. Hydroxylation is carried out by FIH1 (factor inhibiting HIF1), which is a key regulator of the cellular oxygen sensing machinery, and the reaction is dependent on oxygen levels. This raises the exciting hypothesis that cellular oxygen levels determine the activity of the UBD and thus may regulate Cezanne function. Whilst asparagine hydroxylation has long been established as a powerful tool for regulating protein interactions, very little has been known about its role in the ubiquitin system. The results reported by Anja’s group therefore add an important piece to the puzzle. The publication was top-rated and is featured as the Editors’ Pick, highlighting the impact on the field.

Link to Editors’ Pick Highlight.
Link to publication.
Link to Author profile: Julia Mader.
Link to Bremm group.


The cover image was designed by Ella Maru Studio and shows an artistic interpretation of the inhibition of ubiquitin (turquoise) binding to the ubiquitin-binding domain in Cezanne (magenta) by oxygen-dependent hydroxylation.


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4th December 2019 – mePROD proteomics enables measurement of acute translational changes. As published in today’s online issue of Molecular Cell, the Münch Group added signal amplification to dynamic SILAC-driven multiplexing proteomics, resulting in a quantum leap with respect to detection of small signal changes. They dubbed their new method as “mePROD” proteomics – for multiplexed enhanced proteins dynamics – and showed that it enables precise and in-depth quantification of nascent protein chains shortly after labeling. Technically, the signal amplification was achieved by adding a booster channel that increases the signal of interest in a sample. mePROD provides with unprecedented insight into minute translational changes occurring e.g. after stress signals. It is a highly sensitive approach which comes at a low cost and adds a completely new layer of information, therefore complementing established methods for translatome analysis like Ribo-Seq. In addition, it is applicable in situations where sample size is limiting, as it needs only about 100,000 cells.

The team around Christian Münch utilized the technology to solve one of the longstanding conundrums in cellular stress response research. They showed that the two pathways of the integrated stress response (ISR) and mTOR inhibit the same translational targets. Target specificity is driven by global translational status and not by the upstream pathway triggered.

Link to publication
Link to German Press Release.
Link to English Press Release.


Frank Bonzelius Excellence in Teaching

26th November 2019 – Frank Bonzelius receives “Excellence in Teaching” Award. In recognition of the comprehensive redesign and modernization of the biology lecture and courses for medical students, Frank Bonzelius today received the Frankfurt Medical School’s most prestigious Teaching Award. The award is endowed with 25,000 €. Over the past years, Frank took the lead in tailoring all teaching material to the digital era. Everything was optimized for smartboard presentation, iPads were introduced for live-analysis of microscopic images and along the lines of a blended-learning scenario, several interactive eBooks were created. It is not the first recognition Frank receives for his outstanding engagement in teaching. He has repetitively been suggested by students for various awards, and has been honored with an award for “Outstanding dedication to teaching” in 2011 by the Frankfurt Medical School.


sfb 1177 logo 1

25th November 2019 – Successful prolongation of CRC 1177 As announced today by the German Research Foundation (DFG), the Collaborative Research Centre (CRC) on selective autophagy will be funded for another four years. The Centre was established in 2016 under the lead of IBC2 Director Ivan Dikic with partners in Frankfurt and Mainz. It was the first consortium in Germany that started to systematically address challenging questions in autophagy, focussing on the molecular determinants of selectivity, the context-dependent roles of autophagy and its impact on pathophysiology and therapy of human diseases. For the 2nd funding period, the consortium plans to continue its successful path to better understand the mechanistic regulation of autophagy networks in health and disease. To deliver the ambitious and highly integrative work program, access to state-of-the-art technologies is critical for many projects, and the consortium plans to expand the existing platform for quantitative proteomics to include modeling and simulation methods. In addition, new platforms for genomic and chemical screening and for quantitative phenotype analysis will be established. To close the gap on missing expertise, the team was significantly expanded with colleagues from other German institutions. Besides Goethe University, the Universities of Mainz, Tübingen, Freiburg and Munich, the Max Planck Institute of Biophysics, the Institute of Molecular Biology in Mainz and the Georg Speyer Haus in Frankfurt are involved in the 2nd funding period.


Link to CRC 1177/SFB 1177
Link to German press release


Highly Cited Researcher 2019 news

19th November 2019 – Ivan Dikic amongst the most influential scientific minds. Today, the Web of Science Group released its annual list of Highly Cited Researchers. On it is IBC2 Director Ivan Dikic, who is recognized for his outstanding record in the field of Molecular Biology and Genetics. The list was curated by analyzing highly-cited papers published between 2008 and 2018. According to the definition, a highly-cited paper is one that at the end of 2018 ranked in the top 1% by citations in a given field and year. Based on the total count of citations for those papers, researchers are then ranked, and the top 1% in each field are selected for the list. By this method, scientists are identified who have published multiple highly-cited papers and who therefore have significant and broad influence in their field. It is the second year in a row that Ivan is on the list, in 2018 he was recognized in the Cross-Field section. Congratulations to Ivan!


Link to the Highly Cited Researchers List 2019.


FEBS Poster Prizes Kevin Klann

19th November 2019 – Kevin Klann awarded with FEBS Journal poster prize. Kevin Klann, PhD student in the Münch lab, was awarded with one of two FEBS poster prizes during the EMBO Proteostasis Meeting in Ericeira, Portugal. During the meeting, Kevin presented exciting novel insight on how the cellular translatome is shaped by proteotoxic stress. The data was generated using a novel mass spectrometry method recently developed in the Münch group. This method enables the quantitative analysis of small changes in protein synthesis level that e.g. occur following proteotoxic stress. The prize is endowed with €200 and sponsored by the FEBS Journal. Congratulations to Kevin!



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5th November 2019 – Novel enzyme class counteracts PR ubiquitination Phosphoribosyl-serine (PR) ubiquitination is a novel type of ubiquitination utilized by Legionella pneumophila during infection. In the past three years, IBC2 Director Ivan Dikic and his team were amongst the front-runners in unravelling the exciting chemistry behind. Now they add a new piece to the puzzle: As reported in today’s online issue of Molecular Cell, they discovered two bacterial effectors which are capable of removing PR ubiquitination. According to their function, they named the proteins as DUPs: DeUbiquitinases for PR ubiquitination. They continued to elucidate the catalytic mechanism of DUPs, providing detailed structural understanding of yet another novel chemistry. In a next step, they utilized a mutant DUP form to trap and identify PR-ubiquitinated cellular components. This is the first systematic identification of targets for PR ubiquitination, and it will provide unprecedented insight into the host-pathogen interaction upon Legionella infection. Donghyuk Shin, researcher in the Dikic group, comments: “It is surprising how this bacterium uses completely new chemical reactions to attack host cells. Many Legionella proteins remain unknown and need to be explored. We hope our studies provide new approaches to develop novel antibacterial reagents.” Legionella pneumophila causes Legionaries’ disease which presents with an atypical form of pneumonia and may be fatal in elderly and immunocompromised patients.


Link to publication


Ivan Dikic gives Leibniz Lecture at NIH

23rd October 2019 – Leibniz Lecture organized by German Research Foundation (DFG) Ivan Dikic, recipient of Gottfried Wilhelm Leibniz Prize in 2013, gave a Leibniz Lecture on "Ubiquitin and Autophagy networks in Health and Disease" at the National Institutes of Health (NIH) in Bethesda (MD, USA) on 23rd October 2019. The Leibniz Prize is the highest honor awarded in German research. Established in 1985, the prize provides an unparalleled degree of freedom to understanding scientists and academics to pursue their research interests. The DFG organizes Leibniz Lectures in different regions across the world in order to promote the prize, the research conducted by the prize holders and the high quality of German science in general.





Ivan Dikic Elected to the American academy of Arts and sciences

10th October 2019  – Ivan Dikic elected to the American Academy of Arts and Sciences Professor Ivan Dikic, Director of the Institute of Biochemistry II at Goethe University Frankfurt, has been inducted to the venerable American Academy of Arts and Sciences. Since 1780, the Academy has regularly been electing new members to recognize their outstanding achievements in academia, the arts, business, philanthropy, and public affairs, in line with founders’ vision “to cultivate every art and science which may tend to advance the interest, honor, dignity, and happiness of a free, independent, and virtuous people.” Academy members are world leaders and represent the most innovative thinkers in their fields. Amongst them are more than 250 Nobel and Pulitzer prize winners.

I am deeply honored to join this circle of distinguished personalities,” Dikic said. “My gratitude goes to all past and present members of my lab, my mentors, and colleagues at Goethe University and to my family for their enduring support and friendship.” Being passionate about science and education, he also took the opportunity to send a message to the next generation: “I wish to stress that science is an amazing profession where we can freely explore new ideas, enrich our creativity by curiosity, benefit society and have fun by sharing knowledge and working together with students and colleagues around the world.” Ivan Dikic is after philosopher Jürgen Habermas the second member of Goethe University to receive this great honor. He has been elected as one of 23 international honorary members this year in the field of biological sciences, acknowledging his work in deciphering the role of ubiquitination and autophagy as quality control pathways in cells.

One of the reasons to honor extraordinary achievement is because the pursuit of excellence is so often accompanied by disappointment and self-doubt,” said David W. Oxtoby, President of the American Academy of Arts and Sciences. The Academy’s members include Benjamin Franklin (elected 1781), Charles Darwin (1874), Albert Einstein (1924), the anthropologist Margaret Mead (1948), the economist and Nobel Prize winner Milton Friedman (1959), Martin Luther King, Jr. (1966) and actor John Lithgow (2010).

The induction ceremony took place from 11th to 13th October in Cambridge, MA (USA).



Christian Münch honored by Aventis Foundation

12th September 2019 – Christian Münch honored by Aventis Foundation In a festive ceremony embedded in Goethe University’s Postdoctoral Day, IBC2 group leader Christian Münch today received the Aventis Foundation Postdoctoral Award. The award is endowed with € 100,000 and intended to support young academics on their track towards full professorships. Each year, the Aventis Foundation cooperates with a scientific institution to honour up to three of the most outstanding talents in life sciences. This year, besides Christian, two colleagues working at Goethe University’s Riedberg campus have been selected, Daniel Merk and Inga Hänelt.

Christian started his Emmy Noether group at IBC2 three years ago after returning from Harvard Medical School to Germany. He has been extremely successful in securing independent funding, e.g. holds one of the prestigious ERC starting grants. His group aims at better understanding the molecular mechanisms driving mitochondrial quality control. Despite being fully devoted to basic science, Christian’s research has direct relevance to common neurodegenerative diseases.

Pictures taken by Uwe Dettmar.

Link zu GU Press Release
Link zu GU News
Link zu Bericht der Aventis Foundation



        Legionella controls its toxicit

22nd July 2019 – Mechanism of Legionella toxicity control revealed Legionella pneumophilia releases hundreds of enzymes that are instrumental for its propagation and subversion of the hosts’ immune system. Some of these virulence factors are extremely toxic, and their action needs to be strictly controlled to not kill host cells immediately. A team of scientists from IBC2 and EMBL Grenoble has now analyzed how Legionella keeps the family of SidE effectors in check and made a surprising discovery: They found that a glutamylase activity in regulator SidJ does the job. SidJ attacks the central glutamate of SidE enzymes to attach chains of glutamate, thereby inhibiting SidE activity and limiting toxicity. So far, little is known about glutamylases. “Glutamylation as a protein modification is understudied. Our finding that bacteria uses glutamylation during infection certainly argues for more research in this field“, commented first author Sagar Bhogaraju, who is a former member of IBC2 and now leads a group at EMBL Grenoble. “This is a typical example of how completely unpredictable results drive research. Such discoveries are what make science a fascinating and exciting profession,” added IBC2 director Ivan Dikic, who led the interdisciplinary team. The researchers also revealed how SidJ is selectively activated in host cells: It requires the calcium-binding protein calmodulin which is present in mammalian cells. The now discovered mechanism opens up new possibilities for inhibiting the spread of Legionella in the host organism. “We’re currently working on selectively eliminating SidJ by developing inhibitors for the glutamylase domain. In addition to the use of antibiotics, they could prevent the spread of Legionella pneumophilia in phagocytes,” explains Dikic.


Link to publication in Nature
Link to German press release
Link to English press release


            tackles cellular defense mechanisms

10th July 2019 – A tug of war: how Salmonella tackles cellular defense mechanisms Bacterial pathogens present a major public health concern, especially given the increasing emergence of antibiotic-resistant strains. As such, understanding the molecular details governing bacterial infection is of prime importance. A group of researchers from the Dikic group at IBCII and the group of Danielle Malo at McGill University (Canada) recently joined forces and today, published a first collaborative article in Nature Microbiology. Their study focuses on non-typhoidal Salmonella infections caused by Salmonella Typhimurium, a food-borne bacterial pathogen that infects the intestinal tract.

It was mainly motivated by the clinical implications of these infections, with non-typhoidal Salmonella accounting for approximately 93.8 million illnesses and 155,000 deaths worldwide per year. Through adopting a multi-disciplinary approach, the researchers were able to uncover an important host protein, which they named CYRI that is implicated in combating Salmonella infections. They revealed how Salmonella fights back by reducing the levels of this protein upon infection. Interestingly, they also outlined a protective role for CYRI in infections mediated by Mycobacterium tuberculosis and Listeria monocytogenes. This demonstrates that CYRI drives important signalling events that are relevant in the context of infections by different intracellular bacterial pathogens.

Link zu GU Press Release
Link zu GU Press Release



2019 06
            Đikic Honorary

14th June 2019 – Ivan Dikic receives honorary doctorate from Split University IBC2 Director Ivan Dikic received a honorary doctorate from Split University in a festive ceremony today, acknowledging his exceptional contribution to promoting science at Split University. Since 2002, Ivan has built strong links with Split University’s School of Medicine, being a professor from 2002 till 2017, organizing multiple scientific events, promoting an active exchange and scientific collaborations with GU Frankfurt and – until recently – sustaining an outstation laboratory. The shared passion for science of Frankfurt- and Split-based scientists has led to several high-impact publications already, with more to come. “Looking back I am feeling proud on what we achieved together with colleagues and friends from Frankfurt and Split Universities”, commented Ivan who felt truly touched by receiving the honorary doctorate, which is also the first in his career.

Link zu GU Press Release


Dikic Ivan

17th April 2019 – Ivan Dikic elected a member of American Academy Today, the American Academy of Arts and Sciences announced the election of its new members for 2019. Amongst them is IBC2 director Ivan Dikic. Since 1780, the Academy has regularly been electing new members to recognize their outstanding achievements in academia, the arts, business, philanthropy, and public affairs, in line with founders’ vision “to cultivate every art and science which may tend to advance the interest, honor, dignity, and happiness of a free, independent, and virtuous people.” Academy members are world leaders and represent the most innovative thinkers in their fields. Amongst them are more than 250 Nobel and Pulitzer prize winners. “I am deeply honored to join this circle of distinguished personalities. My gratitude goes to all past and present members of my lab, my mentors, colleagues at Goethe University and around the world and to my family for their enduring support and friendship”, commented Ivan after he was informed about his election. Being passionate about science and education, he also took the opportunity to send a message to the next generation: “I wish to stress that science is an amazing profession where we can freely explore new ideas, enrich our creativity by curiosity, benefit society and have fun by sharing knowledge and working together with students and colleagues around the world.” Ivan is after philosopher Jürgen Habermas the second member of Goethe University to receive this great honor. The new members will be inducted at a ceremony in October 2019 in Cambridge (USA).

Link zu GU Press Release
Link zu GU Press Release
Link zu GU Press Release


6th March 2019 – 3Cs technology opens new horizons for production of highly complex CRISPR/Cas libraries. As published today in eLife, a team around IBC2 Group Leader Manuel Kaulich has developed a new technology for generating CRISPR/Cas gene perturbation reagents. They dubbed their innovation as “3Cs”, as gRNA are synthesized as covalently-closed circles. It enables the fast and, most importantly, cloning-free production of gRNA and shRNA libraries. By this, the 3Cs technology overcomes one of the major caveats of conventional library production. Another advantage is that the 3Cs technology uncouples sequence diversity from sequence distribution, thereby removing an often-observed bias in the production process and rendering high quality reagents in any order of magnitude. Groundbreaking discoveries can hardly ever be planned, and this one came over a coffee break. Manuel and Andreas Ernst, who at that time also headed an IBC2 group, were talking about their different areas of expertise, and suddenly the idea emerged on how to elegantly combine strategies used in phage display with gene editing. With support of Innovectis GmbH, Goethe University’s Tech Transfer Office, they immediately applied for patent protection. To prove performance of 3Cs gene editing reagents in cells, together with the group of IBC2 Group Leader Anja Bremm a library targeting all human deubiquitinating enzymes (DUBs) was produced and their function for cell fitness identified. Then, the team around Manuel went on to generate the largest gRNA library known to date. This so-called oTGW (optimized truly genome wide) library targets 16.5 million unique sites throughout the human genome, both in coding and non-coding regions. The oTGW library has a great potential to fuel future functional genomics studies and is available for the scientific community via the Goethe University Depository. Together with IBC2 Director Ivan Dikic, Manuel set up the Frankfurt CRISPR/Cas Screening Center (FCSC)

Link zu GU Press Release
Link zu GU Press Release
Link to the Research Groups of Link zu GU Press Release and Andreas Ernst



23rd January 2019 – Christian Münch appointed as member of the Johanna Quandt Young Academy at Goethe (JQYA). IBC2 group leader Christian Münch was recently admitted as a member to the JQ Young Academy. Within the “Science funding” program of JQYA, Christian will now receive financial support for his independent research group until October 2023. The Münch group is deciphering quality responses upon mitochondrial protein misfolding, a field with very high biomedical impact. Misfolding of mitochondrial proteins occurs e.g. as part of neurodegeneration, and little is known about how cellular response mechanisms contribute to the onset of respective diseases and their progression. The JQYA is an independent academy within Goethe University which foster researchers at the start of their independent careers.

Link zu GU Press Release


19th December 2018 – Humboldt Research Fellowship for Rukmini Mukherjee. Rukmini Mukherjee was awarded with one of the prestigious Research Fellowships from the Alexander von Humboldt Foundation, which enable postdoctoral researchers from abroad to pursue their next career step in Germany. The proposed project focuses on a selective autophagy process which targets the endoplasmic reticulum (ER phagy). The molecular events driving ER phagy still remain elusive, but it is well known that the reticulon family of proteins (RTNs) plays a key role in the process. Rukmini’s project now aims at deciphering the molecular function of reticulons in ER phagy using high resolution microscopy and biochemistry.
Rukmini received funding for 24 months and will be situated in Ivan Dikic’s lab at Link zu GU Press Release. The Humboldt Foundation strongly supports early-career scientists of all nationalities and scientific disciplines who wish to gain research experience in Germany, and grants approximately 450 - 500 Research Fellowships for postdoctoral researchers and experienced scientists annually.

Link zu GU Press Release


27th November 2018 – List of Highly Cited Researchers released. IBC2 Director Ivan Dikic is one of the worlds’ most influential scientists as revealed by Clarivate Analytics’ Highly Cited Researchers List. He has been selected for his exceptional performance in the newly introduced category “Cross-Field”, based on his multiple high impact papers published across several fields.
The methodology used by Clarivate Analytics to curate this annual list aims at identifying scientists who have substantial contemporary impact. It is calculated from the number of highly cited papers produced, with a highly cited paper being defined as ranking amongst the top 1% as measured by citations for the field and year. Approximately 6,000 researchers worldwide are named in this years’ list. The papers analyzed were published between 2006 to 2016.
Besides Ivan Dikic, 12 other colleagues from Goethe University have been credited by the 2018 list. With this result, Goethe University is second best in Germany, only Heidelberg University scores higher. The global pole position is traditionally taken by Harvard University.

Link to the list
Link zu GU Press Release
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26th November 2018 – DFG approves CRC 1361 on DNA repair and genome stability. The genetic information in our cells is at constant risk of damage, and sophisticated DNA repair mechanisms have evolved to maintain genome stability. Whilst many of the mechanisms have been studied in molecular detail, their regulation and concerted action is still unclear. A new collaborative research center (CRC 1361) on this topic has now received funding from the German Research Foundation (DFG). Under the leadership of Prof. Helle Ulrich of Johannes Gutenberg University Mainz (JGU), scientists from Institute of Molecular Biology gGmbH (IMB) in Mainz, Technische Universität Darmstadt, Ludwig-Maximilians-Universität München, and Goethe University Frankfurt have joined forces to establish a new research hub in this biomedically highly relevant field. The CRC will receive initially about 10 Mio Euro for four years. At IBC2, the group of Ivan Dikic will participate with a project focusing on the replication stress response. The team will analyze mechanisms removing damages like DNA-protein crosslinks which would otherwise result in stalling of replication forks, and will look into cellular strategies of telomere replication.

Link to English press release by JGU Mainz
Link to German press release by JGU Mainz
Link to Press Release by Goethe University
Link to DFG press release
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October 2018 – Ivan Dikic is appointed as Max Planck Fellow. As announced by the Max Planck Institute (MPI) of Biophysics today, IBC2 Director Ivan Dikic has been appointed as Fellow of the Max Planck Society and will start his 5-year-term immediately, including supervision of a small working group at the Frankfurt-based Institute. The Max Planck Fellow Programme has been set up to strengthen cooperation between outstanding university professors and Max Planck Society researchers.
Research in the Dikic group is centered around two major cellular quality control pathways: the ubiquitin system and autophagy. As such they provide protection against various human diseases and are involved in almost all cellular signaling processes. The group covers a wide range of expertise to reveal structure-function relationships. Recently, the Dikic group revealed a novel ubiquitination mechanism induced by bacterial enzymes upon infection of human cells. In collaboration with colleagues at the MPI of Biophysics, the group now aims to resolve additional atomic details of this serine ubiquitination. A second area of mutual interest is in remodeling of endoplasmic reticulum via a process known as ER-phagy. Until now, very little is known about the mechanisms facilitating membrane targeting, bending and shaping during this selective form of autophagy.
In addition, Ivan aims to also build strong links between colleagues at the MPI of Biophysics and the highly competitive cancer research programme at Goethe University. He is one of the founders of the Frankfurt Cancer Institute (FCI), which has recently received significant funding for building up a LOEWE center and a new research building.

Link to the Max Planck Institute of Biophysics
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27th July 2018 – ERC Starting Grant for Christian Münch. The European Research Council (ERC) awarded one of its prestigious Starting Grants to Emmy Noether group leader Christian Münch. The grant provides € 1.44 Mio to carry out a challenging project dubbed ‘mitoUPR’, in which Christian plans to unravel the impact of the mitochondrial unfolded protein response (UPRmt) on the cellular environment in mammalian cells. The UPRmt is a poorly understood mitochondrial stress response that activates upon protein misfolding in mitochondria. Münch’s interest in protein quality control processes dates back to his PhD at University of Cambridge (UK), when he was the first to describe the prion-like behavior of mutant SOD1 in ALS. During his postdoctoral tenure at Harvard University (Boston, USA), he discovered a new branch of the UPRmt controlling mitochondrial translation. Within his ERC project, Christian now plans to analyze how the UPRmt influences processes outside the mitochondrion. According to his central hypothesis, the regulation of cellular stress responses is centrally integrated, and he plans to unravel the role of UPRmt within those signaling networks. A second focus is on mitochondrial RNA granules, which are commonly associated with the organelle’s protein production machinery. Despite the fact that mutations in components of those granules are commonly associated with disease, so far little is known about their architecture and especially their regulation upon stress. To achieve his challenging aims, Christian relies on a range of technologies established at IBC2 and aims at developing an in vivo model for studying the UPRmt.

Link to press release of ERC
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02th July 2018 – IBC2 scientists participated in the 68th Lindau Nobel Laureate Meeting. Once every year, around 30 Nobel Laureates convene at Lindau to meet more than 500 young scientists from all over the world. This year, Hadir Marei, Sissy Kalayil and Sagar Bhogaraju, three postdoctoral scientists from IBC2, have been selected for the 68th Lindau Nobel Laureate Meeting, dedicated to Physiology and Medicine. “It was an unforgettable experience exchanging with scientists from all parts of the world, different generations and backgrounds and having the chances to meeting so many Nobel Laureates at one place”, was the résumé of all three researchers.

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23rd May 2018 – Complementing conventional antibiotics:
Frankfurt scientists reveal atomic details for one of Legionella’s enzymatic weapons and develop first inhibitor.
Antimicrobial resistance (AMR) is a major medical problem worldwide, impacting both human health and economic well-being. Scientific efforts are underway to achieve better control of infections. One promising approach is to limit damage to host cells and tissues in the course of a bacterial infection by blocking the microbial processes that cause such damage. In today’s online issue of Nature, the laboratory of IBC2 Director Ivan Dikic reports a breakthrough substantiating the feasibility of this novel strategy. The scientists solved the structure of the catalytic core of Legionella toxin SdeA. Sissy Kalayil, who is one of the lead scientists on the project, comments: “We reveal atomic details of this mechanism, which now make the rational design of inhibitors possible.” Legionella are known to cause pneumonia and are especially dangerous for immunocompromised patients. The team also showed how this bacterial effector probably chooses its victim proteins within the host cell, exerting its effect by attaching ubiquitin to them. They also developed a first inhibitor blocking the reaction in vitro. “Our basic discovery has allowed us to prove that these enzymes are druggable,” Dikic comments. “But it is early days. There is a long road ahead of us before we will be able to use this novel mechanism therapeutically. And we will surely not stop here.”

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Link to Nature News & Views
Link to German press release
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9th April 2018 – Autophagy: about big hopes, mechanistic insights and realism in drug targeting. Autophagy is deregulated in cancer, neurodegeneration, and many other human diseases. Around the globe, laboratories are revealing more and more mechanistic details on this versatile recycling machinery. “Autophagy currently enjoys star status”, writes IBC2 Director Ivan Dikic in his latest review on the topic. Together with colleague Zvulun Elazar from Weizmann Institute of Science (Rehovot, Israel), he has now given a comprehensive overview of the medical implications of autophagy, published online in Nature Reviews Molecular Cell Biology. As so often in biomedicine, it is a story about unprecedented mechanistic insights, a huge dependency on context, an awful lot of crosstalk, and – last not least – an enormous potential for therapeutic intervention.
Link to publication via SharedIt. An access free version will also be available online on the journal’s website in June.

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12th March 2018 – Volker Zickermann appointed apl-professor. IBC2 group leader Volker Zickermann was appointed as apl (“ausserplanmässiger”) professor at Goethe University (GU). Volker studied biochemistry at the University of Hannover and obtained his PhD at GU Frankfurt. He then moved to the group of Mårten Wikström in Helsinki where he started to work on respiratory complex I, at that time, however, concentrating on the enzyme complex from bacteria. Upon his return to Frankfurt, he joined the laboratory of Ulrich Brandt where he successfully took on the heroic challenge to solve the structure of mitochondrial complex I (Hunte et al., Science 2010; Zickermann et al., Science 2014). In parallel, he completed his habilitation and received his venia legendi in biochemistry. In 2013, he joined IBC2 as an independent group leader. Volker has published more than 50 manuscripts, many of which in highest impact journals (h-index 27). His work has significantly advanced our understanding of molecular mechanisms driving the respiratory chain in higher eukaryotes and is of relevance for neuromuscular and neurodegenerative diseases. Congratulations to Volker!

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28th November 2017 – Georg Voelcker receives Teaching Award. One of this years’ faculty awards for teaching commitment was awarded to Georg Voelcker, who has been lecturing at the IBC2 since 1972. After his retirement, he still actively participated in the education of medical students, and was now honored for his outstanding contribution to the 4th semester biochemistry seminar. “Students attending this seminar already know a lot about biochemistry. But they have no idea how this knowledge can be applied when treating patients”, comments the awardee. “Therefore, I present clinical cases for each biochemical topic touched within the seminar.” To stick to clinical reality, Georg Voelcker has taken on the effort to rework already published cases from the scientific literature to fit to the biochemistry curriculum. When asked for the energy source driving his dedication towards the next generation of medics, Georg Voelcker smiles and comments: “I simply love teaching. The commitment comes very easy if one has the opportunity to work for over 40 years with motivated, intelligent and hard-working students.” The award ceremony took place as part of the 2017 Dies Academicus of the Goethe University Medical School.

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Design by Käthe Schönle

16th November 2017 – Autophagosomal content profiling reveals novel mitophagy pathway. Until now, little was known about the identity of proteins which are disposed via autophagy. In an unbiased approach to shed light on this conundrum, the Behrends group used a novel proteomics technology to selectively capture all cargo proteins carried by autophagosomes in living cells. The outcome was a long list of 1,147 proteins – amongst them numerous involved in mitochondrial function, a rather unexpected result considering that no treatment triggering mitophagy was applied. The researchers followed up on this and made a yet more surprising discovery: They found that proteins from several mitochondrial subcompartments are directed towards autophagosomes in a piecemeal fashion, meaning without degradation of the entire organelle. This establishes a novel mechanism of mitophagy, which may function to maintain the mitochondrial household under basal growth condition. The study was largely funded by the CRC 1177 ( and carried out at IBC2 and at Ludwig-Maximilians-Universität (LMU) München, to where the Behrends lab recently moved. The results are published in today’s issue of Molecular Cell.

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Contact details of Christian Behrends at LMU München
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29th September 2017 – Emmy Noether Grant for Christian Münch. IBC2 group leader Christian Münch receives one of the prestigious Emmy Noether Grants from the German Research Foundation (DFG). His project aims at deciphering the mitochondrial unfolded protein response (UPRmt) in mammalian cells and will be funded with 2 Mio Euros for up to 5 years. Until now, the signaling network determining the UPRmt has remained largely elusive. During his postdoctoral tenure at the Harper lab in Harvard, Christian provided novel insight into this important quality control mechanism, and discovered an entire new branch of the UPRmt controling mitochondrial translation. The funding granted by the DFG now allows him to independently develop his research in this field.

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1st September 2017 – Congratulations: Stefanie Oess takes up professorship at MHB Theodor Fontane Stefanie Oess was appointed as Chair of Biochemistry at the Brandenburg Medical School Theodor Fontane. Within the still young university, Stefanie will play a critical role in shaping the biochemistry curriculum for students. In parallel, she will be continuing to push forward her challenging and unique research program in cardiovascular signaling. The Oess laboratory will be situated within newly built premises on Campus Brandenburg, with Meike Hoffmeister as laboratory head overseeing all scientific operations. After many years of shared scientific adventures and personal memories it is with mixed feelings that the IBC2 says farewell to Stefanie and Meike. We are losing not only great scientists, but also great personalities who have grown to be good friends. Congratulations to both of them for their new positions and we hope to see them back in Frankfurt occasionally!

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4th July 2017 – DFG approves FOR application. Today, the German Research Foundation (DFG) announced the establishment of a new Research Unit (FOR 2625) on the mechanisms of lysosomal homeostasis. The Unit is led by Thomas Braulke from the University Medical Center Hamburg-Eppendorf, with 13 research groups from Germany and one from The Netherlands taking part. From IBC2, Anja Bremm and Ivan Dikic are on board, bringing in their expertise in ubiqiuitin signaling and deciphering how ubiquitin regulates lysosome function. The overall aim of the Unit is to analyze biogenesis, function and turnover of lysosomes with the ultimate goal to better understand the pathophysiology of lysosomal disorders and develop novel therapeutic strategies. Funding for the Lysosome Research Unit has been granted initially for three years with an option for prolongation.

Link to DFG press release.
Link to the Braulke group.
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7th July 2017 - Nosip controls brain development in mouse and Xenopus. The IBC2 research group of Stefanie Oess recently discovered that the protein Nosip is crucial for the function of neural stem/progenitor cells and thus critical for the complex process of brain development. In previous work, the group had already elucidated that the E3 ligase Nosip is a regulator of forebrain and craniofacial development in mice. In their latest study, the researchers now combined in vivo and in vitro techniques and applied state-of-the-art proteomics to describe a novel function of Nosip upstream of Retinol-binding protein 1 (Rbp1) in early neurogenesis. Using an interdisciplinary approach combining the two model systems of mouse and Xenopus, the team of Stefanie Oess in collaboration with the group of Susanne Kühl from the University of Ulm have elucidated the role of Nosip as critical factor for neural stem cell/progenitor self-renewal and neurogenesis. The study contributes to a more detailed understanding of developmental neurogenesis and provides knowledge needed for the design of novel therapeutic strategies for central nervous system repair. The results have now been published online in Developmental Biology (Hoffmeister et al, 2017).

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Photographer: Regina Brodehser

16th June 2017 – MSCC Poster Prize 2017 for Rahel de Bruyn. Rahel de Bruyn from the Kaulich group is one of the winners of this years’ poster prize at the 8th Mildred Scheel Cancer Conference (MSCC) in Bonn. She was awarded for her outstanding work on the tumor suppressor RB1 which controls cell cycle entry. If a cell is not ready for DNA replication, RB1 halts further progression of the cell cycle in G1 phase. Thereby, it prevents the replication of damaged DNA which may lead to detrimental mutations and cancer development, as seen in retinoblastoma patients who carry a mutated RB1 gene. Besides causing retinoblastoma, this gene has been implicated in the etiology of numerous other cancers.
The MSCC is organized by the German Cancer Aid (Deutsche Krebshilfe). This year the conference focused on novel therapeutic strategies, metastasis and cancer genetics. Three poster prizes of 1,000 € each were given to honor the most excellent work presented.

Link to conference
Link to announcement of German Cancer Aid (Deutsche Krebshilfe)
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15th June 2017 – RTN3 identified as novel ER-phagy receptor. The endoplasmic reticulum (ER) is the cell’s largest and probably most versatile organelle. It consists of extended membrane structures, which are constantly remodeled to ensure functionality in all cellular states. Degradation of the ER is mediated by a specialized form of selective autophagy (ER-phagy), a process which is until now not very well understood. An international team around Ivan Dikic has identified Reticulon 3 (the full-length form of RTN3) as a selective receptor which specifically triggers fragmentation of ER tubules and their delivery to lysosomes. The process requires the core autophagy machinery but is independent of FAM134B, the first ER-phagy receptor previously identified by Dikic’s group. FAM134B is responsible for targeting ER sheets rather than ER tubules.
The scientists were surprised to discover that the full length RTN3 contains six of the so called LIR motifs that are essential for the function of autophagy receptor. Normally, a single LIR motif is sufficient. Most likely, the high amount of LIR motifs leads to a positive amplification loop. The experiments also enabled a broader view on different roles of the RTN protein family, highlighting the importance of discriminating between isoforms which display highly specialized and unique functions. The results have now been published online in eLife (Grumati et al, 2017).

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15th May 2017 – BUILD.FUTURE.NOW. This was the slogan of a public TEDx event in Zagreb, at which IBC2 director Ivan Dikic shared his thoughts about what can be learnt from bacteria. It was the largest Croatian TED event ever, full of enthusiasm, creativity and inspiration. The 20 speakers came from many different areas of society, and all gave one major motivation message: boundaries can be broken if we just strive hard enough. „It was an amazing event, positive and vibrant. The moment when you step out on stage is almost electrifying“, described Ivan Dikic his appearance in the Lisinski Concert Hall which was filled with an audience of 1000. TED is a non-profit organization devoted to spreading great ideas around the globe, TEDx events are independently organized, but follow the same mission of helping communities to spark conversation and connection

Link to picture gallery.
Link to TEDxZagreb.
Link to TED.
Link to the video on Youtube
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Image: Ella Maru Studio, Cover Design: Karen Moore.

8th May 2017 – Linear ubiquitination controls Salmonella growth. A team around Ivan Dikic and Mike Heilemann (Chemistry Department, Goethe University) gained unprecedented insight into the mechanism by which cells fight Salmonella infections. Upon intracellular invasion, bacteria are usually rapidly surrounded by a coat of ubiquitin, the function of which remained unclear until now. Combining super-resolution microscopy with cell biological analysis, the researchers now discovered that distinct ubiquitin chains transform the bacterial surface into a molecular signalling platform. They were able to visualize the nanoscale distribution of different ubiquitin chains on the bacterial surface. One chain type, so called linear chains, specifically triggers pro-inflammatory signalling cascades, thereby restricting bacterial proliferation. In addition, the researchers identified the deubiquitinase OTULIN as a regulator capable of limiting this reaction – a very important notion considering the fact that excessive inflammation is one of the major causes of tissue damage following bacterial infection.
In collaboration with colleagues from Japan, the Frankfurt researchers now published their results in the latest online issue of Nature Microbiology. Their work is an excellent example for interdisciplinary collaboration and was enabled by funding of several large research networks, e.g. the Cluster of Excellence Macromolecular Complexes, the CRC 1177 on selective autophagy and the LOEWE ubiquitin network. The discovery paves the way for many new projects. Very recently, Ivan Dikic obtained one of the prestigious ERC Advanced Grants in which he will investigate the role of ubiquitin in modulating the host-pathogen interaction in more detail.

Link to publication.
Link to German press release.
Link to English press release.
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3D-dSTORM image of a Salmonella bacterium inside a human cell, surrounded by linear ubiquitin chains. Copyright: Mike Heilemann/Ivan Dikic

7th April 2017 – ERC Advanced Investigator Grant to Ivan Dikic. IBC2 director Ivan Dikic has been awarded with an Advanced Investigator Grant of the European Research Council (ERC). It is the second time that Dikic receives the prestigious grant which entails funding in the amount of € 2.5 million for the next five years.
Within his new project, Dikic is investigating how bacteria manipulate the ubiquitin system of their host organism. "Bacteria are rapidly changing chemical factories that subdue human cells and exploit them for their own needs. We focus on foodborne pathogens such as Salmonella, Escherichia coli and Shigella that cause around 200 million infections and more than 250.000 deaths per year”, explains Dikic. “We will investigate how bacterial toxins containing different enzymatic activities cause cell and tissue damages, eventually resulting in symptoms of infection.”
The ultimate goal is to fully understand the role of the ubiquitin system in bacterial infections and develop new strategies for combating infectious diseases. To this purpose, Dikic is working together with partners in the pharmaceutical sector. “Targeting bacterial toxins is a relatively new approach, which aims at preventing bacterial pathogenicity and works complementary to antibiotics. This is a very critical field of research as bacterial resistance to conventional antibiotics is becoming an alarming medical problem”, comments Dikic.

Link to ERC press release.
Link to GU press release.
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Timurs Maculins H

04th May 2017 – AXA postdoctoral fellowship for Timurs Maculins. Timurs Maculins, postdoctoral scientist in the group of Ivan Dikic at IBC2, was awarded a 2-year postdoctoral fellowship by the AXA Research Fund. The funded project will focus on how pathogenic bacteria hijack the host cell and suppress its immune response, ultimately aiming at finding new antibiotics.
The AXA Research Fund grants 25 postdoctoral fellowships annually for postdoctoral researchers and is dedicated to boosting scientific discoveries that contribute to societal progress. It was established in 2007 and has since then supported more than 500 research projects, hosted in 34 countries, aiming to foster research on risks and challenges today’s societies are faced by.
Link to AXA Research Fund project website
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20th March 2017 – Tracing down linear ubiquitination. Ubiquitin molecules can be attached to each other to build longer chains with unique 3D structures mediating diverse functions. About a decade ago, linear ubiquitin chains, in which the head of one ubiquitin is linked to the tail of another, were identified as a new chain type involved in inflammatory signalling. However, target proteins of linear ubiquitination and their specific functions have largely remained elusive. A novel technology developed by an international team around IBC2 group leader Koraljka Husnjak now enables the systematic analysis of linear ubiquitination targets. Details are published in today’s online issue of Nature Methods.
Together with partners from the University of Tübingen, Queen Mary University and Francis Crick Institute (both London, UK), the Frankfurt scientists modified the ubiquitin molecule in such a way that it maintains its cellular functions whilst at the same time enabling the enrichment and further analysis of its targets by mass spectrometry. With this technology at hand, it is now possible to identify proteins modified by linear ubiquitin. This highly sensitive approach is an important breakthrough that will strongly improve our understanding of the functions of linear ubiquitination and its role in diseases.
Link to publication
Link to GU press release in German
and English
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15th Mar 2017 – TIRR influences DNA double-strand repair through 53BP1. Christian Münch, group leader at the IBC2, contributed to a study recently published in Nature. The work was led by Dipanjan Chowdhury at the Dana-Farber/Harvard Cancer Center and described the role of an uncharacterized protein – TIRR – in regulating DNA double-strand repair. TIRR binds to the tandem Tudor domain of 53BP1, a protein important for DNA double-strand repair, masking the histone methyl-lysine binding motif on 53BP1 and preventing chromatin binding. Also, TIRR stabilizes the nuclear-soluble 53BP1 fraction through direct binding. Through these mechanisms, TIRR affects 53BP1 activity and DNA double-strand repair efficiency.
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Award ceremony, from left to right: Prof. Dr. Roland A. Fischer (Vice President DFG), Dr. Stephan Fuchs (GU), Dr. Heide Genau (GU), Prof. Dr. Brigitte Haar (Vice President GU), Ministerialdirigent Frithjof A. Maennel (BMBF), photographer: Michael Lüder.

1st March 2017 – Award for ‘Let’s talk about UBAUT’. The award ceremony for the 2016 Competition on International Research Marketing Ideas by the German Research Foundation (DFG) took place on 16th Feb 2017 in Potsdam. Besides Goethe University (GU) three other institutions were honored, and the prize was handed over by DFG’s Vice President Prof. Roland A. Fischer in a lively ceremony comprising interviews with all awardees. On the stage for GU were Vice President Prof. Brigitte Haar and project coordinator Dr. Heide Genau, who together presented the concept ‘Let’s talk about UBAUT‘ ( It is based on the biomedical research focus in the ubiquitin and autophagy field in the Rhine Main region and was initiated by the IBC2, LOEWE Ub-Net ( and the SFB 1177 ( Cornerstones of the program are ambassador visits to biomedical institutions in the US as well as a short stipend program for international scientists interested in pursuing a career in Germany.

More information & Call for application.
Link to GU press release.
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6th February 2017 - Fluorescence-based sensors for specifically monitoring autophagy. Autophagy is a cellular recycling and quality control pathway that is essential for maintaining cellular metabolism and homeostasis. Its malfunction contributes e.g. to neurodegenerative diseases and cancer.
Ubiquitin-like ATG8 proteins constitute central components of the autophagic machinery. However, until today, it is not completely clear why yeast harbors only one ATG8 protein while human cells contain six mammalian ATG8 orthologs, classified into the LC3 and GABARAP subfamilies. Using an interdisciplinary approach combining phage display with additional functional biochemical assays as well as cellular biology, the laboratories of Ivan Dikic and Andreas Ernst now engineered a valuable tool for studying specific functions of LC3 and GABARAP proteins. They developed fluorescence-based sensors that are able to discriminate between the six different members of the mammalian ATG8 protein family and track their actions within cells. As first application, the scientists successfully monitored the involvement of LC3C in selective autophagy of mitochondria (mitophagy) and Salmonella (xenophagy). The joint effort of the Dikic and Ernst groups has been published recently in EMBO Journal and will be helpful in decoding biological functions of individual LC3/GABARAP proteins.

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7th February 2017 - Evgenij Fiskin awarded for PhD thesis. Evgenij Fiskin has been selected to receive the 2017 Bayer HealthCare Prize to honor his outstanding PhD thesis, which he completed in the Dikic lab at IBC2. The award is donated by Bayer Pharmaceuticals and bestowed by the German Society for Biochemistry and Molecular Biology (GBM) at the Mosbacher Kolloquium ( Besides, he was also awarded the PhD prize of the German Society for Hygiene and Microbiology (DGHM Promotionspreis) and the Nikon Young Scientist Award of the German Society for Cell Biology (DGZ).
During his PhD, Evgenij analysed the role of ubiquitination in bacterial infection, unveiled dynamic changes in the ubiquitinome upon infection and provided a detailed insight into how Salmonella tricks the immune system.


Most relevant publications:

Fiskin E*, Bhogaraju S* et al. Nat Commun 2017. 8: 14004.


13th Jan 2017 - How Salmonella tricks the immune system. Infections with bacterial pathogens represent a global burden and are a major cause of death worldwide. For the design of new treatment paradigms it is essential to understand the intricate interplay between bacterial virulence strategies and host defense. The Dikic laboratory now added the next piece to the puzzle: They elucidated how the Salmonella effector enzyme SopA, a HECT-like E3 ligase, targets two host proteins involved in activating the immune defense (TRIM56 and TRIM65) and triggers their degradation. Atomic details of this new mechanism have now been published in Nature Communications and give a detailed insight into how Salmonella increases its own infectivity by interfering with the host immune response.
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5th Jan 2017 - IBC II recruits new group leader to establish the Protein Quality Control group. The Institute of Biochemistry II welcomes its new independent group leader Dr. Christian Münch. Dr. Münch joins the IBC II after completing his postdoctoral work at Harvard Medical School. He is an expert on protein homeostasis and quantitative mass spectrometry and will establish the Protein Quality Control group at IBC II. Link to webpage
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20th December 2016 - Humboldt Research Fellowship for Postdoctoral Researchers for Hadir Marei. Hadir Marei, postdoctoral scientist in the group of Ivan Dikic at IBC2, was awarded a 2-year Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt Foundation. The funded project will focus on further elucidating the regulatory interplay between intracellular signaling cascades and the autophagic pathway.
The Humboldt Foundation grants approximately 800 Research Fellowships annually for postdoctoral researchers and experienced scientists through a number of different sponsorship programs to which applicants apply with their own topics and research concepts. Across all scientific disciplines, the Foundation strongly supports junior scientists from abroad wishing to gain research experience in Germany.Link to Humboldt Foundation
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15th December 2016 - DFG funds research on mitochondrial de novo fatty acid synthesis. Recently, Dr. Heike Angerer, postdoc in the Structural Bioenergetics Group at IBC2, received a grant from the German Research Foundation (DFG), enabling her to study the importance of de novo synthesized long-chain fatty acid chains in mitochondria. Heike’s previous work showed that long acyl chains are required for the function of several mitochondrial enzymes, including the essential respiratory chain, sustaining cellular energy supply. In the next two years, Heike aims at understanding the impact of mitochondrial fatty acids on mitochondrial function, since malfunction in this pathway was linked to various human diseases.
Link to Structural Bioenergetics Group
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10th December 2016 - Autophagy captures the Nobel Prize. This year’s Nobel Essay in Cell has been written by  Ivan Dikic (IBC2) together with Sharon Tooze (Francis Crick Institute, London). Published on time for the Nobel Ceremony on 10th December, the article highlights milestones leading to the discovery of the molecular principles underlying autophagy by Yoshinori Ohsumi, who is this years’ winner of the Nobel Prize for Medicine or Physiology. Dikic and Tooze tell the story of a simple yet insightful yeast genetic screen that revealed what later was recognized to be one of the most powerful quality-control pathways in cells.
Link to essay in Cell.
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5th December 2016 - 1,08 M € for prolongation of LOEWE program Ubiquitin Networks (Ub-Net. As the Hessian Ministry for Science and Arts (HMWK) announced today, the LOEWE program Ub-Net will be prolonged for another year. The initiative led by IBC2 Director Ivan Dikic receives 1,08 M € to continue deciphering the complexity of ubiquitin networks and analysing the underlying molecular mechanisms. Ultimate aim is to better understand the role of ubiquitin signalling in cellular homeostasis, in pathogen defence, in embryonic development as well as in ageing and pathophysiology of human diseases. Partners within the network are situated at the Goethe University Frankfurt, the Max Planck Institute in Bad Nauheim and the Georg Speyer House in Frankfurt. The network was initiated in 2014 and received 4,3 M € for the first three years of funding.
Link to HMWK press release
Link to LOEWE Ub-Net website
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01.12.16 Pub

1st December 2016 - New ubiquitin chemistry regulates life processes. In the latest issue of Cell, a team around IBC2 director 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.
Free Access to Cell Paper (until 20th January 2017)
Link to GU press release in German
Link to GU press release in English
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1st December 2016 - International marketing concept of UBAUT networks receives DFG award. 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 IBC2, LOEWE Ub-Net and SFB 1177 on Autophagy 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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21st Nov 2016 - Insights in repairing DNA-protein crosslinks. Genomic instability is a hallmark of cancer and aging. Scientists at Goethe University Frankfurt now discovered the molecular cause for genetic instability in patients suffering from a rare segmental progeroid syndrome named Ruijs-Aalfs syndrome. The syndrome leads to premature aging and early onset liver cancer.
“Until now, it was unclear how these patients, carrying mutations in the metalloprotease SPRTN, succumb to the disease”, comments Ivan Dikic, director of the Institute of Biochemistry II. Dikic’s team has now shown that SPRTN is required for repairing a specific type of DNA damage, so called DNA-protein crosslinks (DPCs). Crosslinks are extremely toxic for cells as they prevent proper chromosome duplication. Cells deficient in SPRTN functions are sensitive to chemotherapeutic treatments which usually induce crosslink formation.
The results reported by the Frankfurt team follow in the footsteps of a breakthrough discovery by the late Stefan Jentsch (Max Planck Institute of Biochemistry, Munich), who was the first to identify a dominant role for the yeast Wss1 protease in resolving DNA-protein crosslinks. SPRTN is now the first mammalian protease for which such an essential function was shown. Moreover, SPRTN cannot functionally complement Wss1 function in yeast, indicating to the presence of a family of DPC metalloproteases with related functions.
The results of this study have been published in eLife online (Lopez-Mosqueda et al.). Two additional reports from the Francis Crick Institute in London (Stingele et al., Mol Cell 2016) and from Oxford University (Vaz et al., Mol Cell 2016) describe similar roles for SPRTN in mammalian DPC repair.
Link to the article


14th Nov 2016 - The AAA ATPase MDN1 Acts as a SUMO-Targeted Regulator in Mammalian Pre-ribosome Remodeling. Raman et al. demonstrate transient SUMO-dependent complex formation between the AAA ATPase MDN1 and PELP1 during 60S biogenesis. They show that SUMO conjugation to PELP1 recruits MDN1 to pre-60S particles, while reversal of this modification by SENP3 is needed for the release of both factors during mammalian pre-ribosome remodeling.

Link to the article



13th Sep 2016 - SUMO Signaling by Hypoxic Inactivation of SUMO-Specific Isopeptidases. The SUMO Signaling Group of IBCII find that SUMO signaling in hypoxia is altered by inactivation of SUMO-specific isopeptidases. Using proteomic analysis, we define a subset of hypoxia-induced SUMO1 targets and propose that hypoxia-induced SUMOylation of the transcriptional co- repressor BHLHE40 contributes to metabolic reprogramming under these conditions.


Award ceremony, from left to right: Prof. Dr. Wilhelm Bender,
Prof. Dr. Birgitta Wolff, Dr. Anja Bremm, Stefan Messer, photographer: Jürgen Lecher.

30th June 2016 - Adolf Messer-Stiftungspreis for Anja Bremm. Dr. Anja Bremm, group leader of the Molecular Cell Biology Group at IBC2 and Buchmann Institute for Life Sciences (BMLS) was awarded the 2016 Adolf Messer-Stiftungspreis for her research on the physiological role of deubiquitinases (DUBs) in autophagy, endowed by the Adolf Messer Foundation. Stefan Müller, professor of IBC2, held the laudatory speech at the official award ceremony on June 30th, 2016.
The prize is conferred annually to early career scientists with an outstanding proven track record to promote pioneering fundamental research projects in natural sciences and medicine and is remunerated with 25.000 €.
Link to Anja Bremm’s research group
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8th July 2016 - Frankfurt Conference on Ubiquitin and Autophagy – thanks to all speakers and participants. span>From July 4th to 7th, 2016, leading experts in Ubiquitin and Autophagy research from around the world were brought together at Goethe University’s Medical Campus for the first Frankfurt Conference on Ubiquitin and Autophagy, jointly organized by the Cluster of Excellence Macromolecular Complexes, the DKTK site Frankfurt/Mainz, the LOEWE program Ub-Net and SFB 1177. Since the ubiquitin system and autophagy are essential for maintaining cellular integrity and homeostasis, and defects in the two quality control systems are involved in the pathogenesis of numerous diseases, the meeting put emphasis on gaining a more global view on cellular quality control mechanisms, their interconnectivities as well as on exploiting the potential for therapeutic interventions. More than 300 scientists from 12 countries attended the meeting and almost 50 talks in five interdisciplinary sessions covered a broad range of topics from the discovery of basic molecular mechanisms to translation into clinical applications. Moreover, the contribution by early career researchers in vivid discussions and more than 110 poster presentations was overwhelming, as was the quality of the work presented. Coffee breaks, welcome reception and a farewell barbecue at Goethe University’s Westend Campus with a view on the impressive Frankfurt skyline fostered the exchange and interaction amongst the participants giving rise to new ideas, collaborations and insights. The organizers would like to thank all speakers and participants for their active and valuable contribution to the meeting and look forward to the next Frankfurt Conference in 2018.


12th May 2016 - Unveiling the ubiquitin fingerprint induced by Salmonella infection. A cellular invasion by bacterial pathogens can immediately be detected on the molecular level. The dynamic changes observed are due to the host cell gearing up for defense and the bacterium trying to achieve its primary goal of propagation. As published in the current online edition of Molecular Cell, the groups of Ivan Dikic and Christian Behrends have shed light on the dynamic changes within a host cell in response to an infection with Salmonella. Like criminal profilers, and using quantitative mass spectrometry, the scientists tracked all sites within the host cells that are ubiquitinated in response to an infection. Ubiquitination is commonly used by cells to relay signals. The scientists hypothesized that all proteins that become ubiquitinated after Salmonella invasion must be involved in either propagating or limiting the infection. Indeed, this novel approach gave an unprecedented insight into all cellular processes affected by the infection and identified important new regulatory hubs. Given the increased occurrence of antibiotic resistance in bacterial pathogens, which hampers current treatment schemes and prompts the need for alternative anti-bacterial strategies, this comprehensive dataset will reveal new targets for inhibiting Salmonella propagation and preventing the associated inflammatory reaction.
Link to full text article
Link to Meet the authors
Link to Autophagic Punctum

  Christian Behrends V

14th Apr 2016 - Boehringer Ingelheim Foundation awards Christian Behrends. Dr. Christian Behrends, group leader of the Autophagy Signaling Group at the IBC2 and part of the SFB 1177 on Selective Autophagy has been selected to be a PLUS3 fellow of the Boehringer Ingelheim Foundation. The foundation will fund his research with a generous support of around 900.000 € for the next three years.
Link to Christian Behrends Lab





29th Mar 2016 - Shedding light on ALS: Novel mechanism in selective autophagy discovered. ALS (Amyotrophic lateral sclerosis) is a rare and severe disease characterized by loss of motor neurons and neurodegeneration leading to death within 3-4 years. The 2014 ice bucket challenge brought ALS to broader public attention but to date there is no treatment for ALS, despite intensive research in the field. After being involved in the discovery of a kinase (Tank-binding kinase 1, TBK1) linked to ALS (Freischmidt el al., nature neuroscience 2015), researchers from the IBC2 in collaboration with international partners now succeeded in clarifying the physiological function of TBK1. The group around Ivan Dikic revealed that TBK1 specifically phosphorylates its adaptor protein optineurin, thereby enabling a stronger binding of optineurin to ubiquitin that marks damaged mitochondria. By this means, TBK1 promotes an important cellular quality control system responsible for the clearance of damaged mitochondria and other cellular organelles, a process called selective autophagy. Damaged mitochondria, TBK1 and optineurin have long been linked to neurodegenerative diseases such as Parkinson’s and ALS. However, the molecular details behind this connection are only beginning to be unveiled. Benjamin Richter, first author of the study, and his colleagues could further show that an ALS-associated TBK1 mutant fails to associate with optineurin and damaged mitochondria representing a possible link to the disease mechanism underlying ALS. The results are published in this weeks’ PNAS Online Early Edition.
Link to full text article



23rd Feb 2016 - LOEWE Ub-Net PhD student and postdoc retreat, Rauischholzhausen, Germany. From 22nd to 23rd of February 2016, the LOEWE Ub-Net as well as associated PhD students and postdocs convened in the historical walls of castle Rauischholzhausen, the seminar house of the University of Gießen. In two days, all students and postdocs presented their projects and the discussion lead was rotated amongst the participants. This created a very interactive and productive exchange of ideas, experiences and advices. New collaborations were established and existing contacts strengthened. Besides, two external guests gave valuable insights into the systems of industry and academia as well as into the world of targeting influenza viruses for therapy. “The retreat is worth a repetition” was the unanimous opinion of the students afterwards.


Registration open now – Frankfurt Conference on Ubiquitin and Autophagy. Together with the Cluster of Excellence Macromolecular Complexes, the SFB 1177, and the DKTK Frankfurt, LOEWE Ub-Net is organizing the first Frankfurt Conference on Ubiquitin and Autophagy in July 2016. Both the ubiquitin system and autophagy are essential for maintaining cellular integrity and homeostasis. Defects in the two quality control systems are involved in the pathogenesis of numerous diseases. The conference brings together leading experts in this field. Further information and registration can be found here.


15th Jan 2016 - Masato Akutsu successful in Volkswagen Foundation funding initiative. Exploring daring new ideas, which may transform common wisdom – this is the aim of the relatively young Volkswagen Foundation initiative called Experiment!. Dr Masato Akutsu, group leader at the IBC2 and BMLS, succeeded in the highly competitive call for bold research concepts. He secured just under 100.000 € to prove a concept which has the potential to revolutionize structure determination by protein crystallography. This process is currently often hampered by the ability of proteins to crystallize. Akutsu now proposes to develop a technology, which overcomes the need for conventional protein crystals. If successful, this will open the avenue for structure determination of a long list of proteins for which high-resolution structures could so far not be obtained.



Manuel Kaulich V

5th Jan 2016 - IBC2 Appoints New Gene Editing Group Leader. The Institute of Biochemistry II (IBC2) recruits new group leader: Dr. Manuel Kaulich will be leading the newly formed gene editing research group. Dr. Kaulich is an expert on cell cycle regulation and CRISPR-Cas9-rAAV gene replacement technologies.



1st Dec 2015 - Teaching Award for Stefanie Oess. Dr. Stefanie Oess, lecturer and independent principal investigator within IBC2, was awarded the 2015 Prize for “Outstanding Dedication to Teaching” of the medical faculty (Preis für besonderes Engagement in der Lehre 2015) in recognition of her project entitled “Introduction of an audience response system in the seminar biochemistry in conjunction with a pedagogic research project”.
The Medical Faculty of the Goethe University Frankfurt awards this prize to promote excellence in teaching and Stefanie was nominated by the undergraduate students attending her biochemistry seminar series. “I am very honoured that the faculty has selected me as one of this years’ awardees. This is a fantastic recognition by the very same students that our seminar series are designed to engage with and stimulate.”, says Stefanie.
Stefanie has shown a strong commitment to high quality teaching over the past number of years. She has a special interest in a Scholarship of Teaching and Learning, teaching innovation and curriculum design. She holds a certificate in higher education didactics and since 2015 is enrolled in the postgraduate degree programme Master of Medical Education (MME-D).


20th Nov 2015 - DFG funds autophagy research network. Scientists from Frankfurt and Mainz have successfully applied for funding to establish a Collaborative Research Centre (CRC)/Sonderforschungsbereich (SFB) on the molecular mechanisms of selective autophagy. Autophagy literally means „self-eating“ and describes a process by which the cell recycles harmful ballast like aggregated proteins, damaged organelles or even bacterial invaders. For the next four years, the centre is funded by the German Research Foundation (DFG) with 11 M €. The initiative is led by Ivan Dikic, and is the first large-scale collaborative network in Germany in this highly competitive field. In the newly established CRC, researchers from the Goethe University, the University Medical Centre in Mainz, the Georg-Speyer-Haus in Frankfurt and the Institute of Molecular Biology in Mainz have teamed up to characterize selective autophagy on the molecular and functional level. This will eventually lead to a better understanding of the role of autophagy in pathophysiology and pave the road for innovative, targeted therapies. The funding by the DFG will now give a powerful impetus for the network, also strengthening the position of the Rhine Main scientists on the international stage. More information on the CRC/SFB can be found under

Link to German press release.
Link to English press release.


02th Nov 2015 - Mini-Symposium on Autophagy with Patrice Codogno and Nicholas Ktistakis. The Frankfurt Autophagy Network (FAN) and the Institute of Biochemistry II (IBCII) recently hosted two scientists studying the process of autophagy with state-of-the-art microscopy techniques. Whereas Dr. Nicholas Ktistakis (Babraham Institute, Cambridge, UK) employs high-resolution microscopy to investigate the early processes at the onset of autophagy, Dr. Patrice Codogno (Institute Necker Enfants-Malades, INSERM, Paris, France) is interested in the interplay of primary cilia with autophagy and on the precise cellular sites where the autophagic machinery assembles. Together, these two scientists gave a fantastic overview about the recent advances and the methods in their labs initiating vivid discussions that continued through the reception afterwards. Dr. Christian Behrends, group leader at IBCII, and Prof. Ivan Dikic, director of IBCII, organized the event.


29th Oct 2015 - EMBO conference „Ubiquitin and Ubiquitin-like modifiers“ in Cavtat, Croatia. From September 18th to September 22nd 2015 the EMBO conference „Ubiquitin and ubiquitin-like modifiers“ was taking place in Cavtat, Croatia. More than 350 participants enjoyed five days of excellent scientific talks, networking and poster presentations in the stimulating atmosphere of the Adriatic Coast.
It was organized by Ivan Dikic, Alexandra Stolz and Rebecca Pfeiffer from the Institute of Biochemistry II. Co-organizers of the meeting were Brenda Schulman (St. Jude Children’s Research Hospital, USA), Frauke Melchior (DKFZ-ZMBH Alliance, ZMBH, Heidelberg, Germany) and Ron Hay (University of Dundee, UK).
There were almost 200 posters displayed with a strong participation of young scientists and a very high quality of the scientific work presented. In more than 50 talks from senior PIs as well as junior group leaders the advances in the field of ubiquitin and ubiquitin-like modifiers were highlighted and it became clear that the field is facing great progress in fundamental discoveries as well as in translating the research into therapeutic applications. Coffee breaks and evening events promoted the networking in a relaxed and beautiful surrounding giving rise to establishing new contacts, collaborations or strengthening the connections already built. An afternoon boat trip to the UNESCO world heritage city Dubrovnik and a guided tour around the ancient city walls completed the social programme which peaked in the farewell party on the last conference day.
12 PhD students and PostDocs and 6 group leaders from the Institute of Biochemistry II attended this exciting conference and presented their work in posters and talks. Overall the contribution and participation in this meeting was overwhelming and the community is looking forward to the next EMBO meeting on ubiquitin in September 2017.


26th Oct 2015 - Institute Retreat at Heilbronner Land.

The beautiful landscape of Heilbronner Land was the destination of choice for this years’s retreat of the Institute of Biochemistry II which took place from April 15th to April 17th 2015. 3 days full of scientific discussions and exchange as well as many opportunities to socialize during common events promoted the interactive spirit amongst the institute members and raised new interactions and collaborations.
Exciting guest lectures by Philip Grote (Institute of Cardiovascular Regeneration, Frankfurt), Daniela Krause (Georg-Speyer-Haus, Frankfurt) and Malte Wachsmuth (EMBL, Heidelberg) as well as a career session with representatives from academia and industry created a stimulating and motivating atmosphere for all 70 participants, ranging from young PhD students to group leaders. Moreover, social events such as wine-tasting at a local winery as well as hiking through the vineyards, canoing on the Neckar and a guided tour through the Audi factory at Neckarsulm completed 3 successful and inspiring days at Heilbronner Land.



19th Oct 2015 - Ivan Dikic elected a member of European Academy. The European Academy (Academia Europaea) announces the list of 248 scientists who were elected to the academy in 2015. Amongst them is Prof. Ivan Dikic, director of the Institute of Biochemistry 2 at the Medical School Goethe University and founding director of the Buchmann Institute for Molecular Sciences (BMLS).
The Academia Europaea was founded in 1988 as a European Academy of humanities, social, physical and life sciences as well as mathematics, engineering and medicine. This broad assembly of disciplines and the pan-European distribution of its members make the Academia unique amongst other national Academies. “I am honored to accept a membership in the European Academy and will be glad to contribute to its scientific and educational programs”, stated Ivan Dikic.
In addition, Ivan Dikic is a member of the German National Academy of Sciences Leopoldina, the Croatian Academy of Medical Sciences and the European Molecular Biology Organization (EMBO).


Oct 2015 - Ivan Dikic appointed as a Senior Editor of eLife

Prof. Ivan Dikic has been appointed as a senior editor of the scientific journal eLife in the area of molecular signalling and quality control pathways. Since 2013, he has been serving on the board of editors of this unique journal, which is driven by a non-profit, researcher-led initiative and is supported by the Howard Hughes Medical Institute, the Wellcome Trust and the Max Planck Society.
Ivan Dikic also serves on the editorial boards of Cell, Molecular Cell, Developmental Cell, EMBO Journal, EMBO Reports, J Cell Biol, BMC Biology, Biochemical Journal, Cell Death and Diff. He is elected as a chairman of the EMBO Publication Committee from 2015-2018.


3rd Oct 2015 - SGRF Excellence in Science Award for Ivan Dikic

Prof. Ivan Dikic receives this years’ SciGenom Research Foundation (SGRF) Excellence in Science Award for his contribution to molecular signalling and biomedicine. The award was presented at the 2015 NGBT Conference in Hyderabad, India, where Ivan Dikic was giving a keynote lecture on ubiquitin and autophagy networks in health and disease. The SGRF is a not-for-profit organization dedicated to promoting science in India. It supports underfunded research initiatives that tackle important scientific and societal challenges, spanning the complete range of disciplines in genomic research from agriculture to human health. The SGRF Excellence in Science Award honours scientists who have made fundamental and pioneering contributions towards basic and translational research.


1st Oct 2015 - TECPR2 links early secretion pathway and autophagy

Hereditary spastic paraplegias (HSPs) are a diverse group of neurodegenerative diseases that are characterized by axonopathy of the corticospinal motor neurons. A mutation in the gene encoding for Tectonin β-propeller containing protein 2 (TECPR2) causes HSP that is complicated by neurological symptoms. While TECPR2 is human ATG8 binding protein and positive regulator of autophagy, the exact function of TECPR2 is unknown. As published in the latest issue of Molecular Cell, the group of Christian Behrends revealed that TECPR2 interacts with the COPII coat protein SEC24D to stabilize components of the COPII coating machinery. In cooperation with lipidated LC3C, TECPR2 is required for maintaining functional ER exit sites and efficient ER export. Moreover, TECPR2-deficient HSP patient cells display alterations in SEC24D abundance and ER export efficiency. Additionally, TECPR2 and LC3C are required for autophagosome formation, possibly through preserving functional ERES. Collectively, these results disclose that TECPR2 functions as molecular scaffold linking early secretion pathway and autophagy.

For the full article click here



23rd Sep 2015 - Poster prize for SUMO modification studies

< Anne Gärtner, PhD student in the group of Prof. Stefan Müller, was awarded with the Nature Reviews poster prize at the EMBO meeting “Ubiquitin and ubiquitin-like modifiers” (Cavtat, Croatia). Anne’s work elucidates the modification of the small ubiquitin-related protein SU MO with an acetyl group and the impact of this post-translational modification on SUMO chain formation and downstream cellular effects. SUMOylation, the covalent attachment of one or more SUMO molecules to a protein, is linked to a variety of processes such as ribosome biogenesis, nuclear transport and transcriptional regulation. It is therefore of great relevance to understand how this process is specifically regulated and modified.


13th Jul 2015 - NOSTRIN regulates cardiovascular function

As reported in today’s online version of Circulation Research the group of Dr. Stefanie Oess has identified the F-BAR protein NOSTRIN as a crucial factor in the development of endothelial dysfunction, hypertension and diastolic heart failure. In this study the authors show that NOSTRIN is necessary for the correct positioning of the muscarinic acetylcholine receptor M3R at the plasma membrane of endothelial cells. In the absence of NOSTRIN the function of the M3R was markedly impaired, resulting in abolition of the calcium response to acetylcholine, an impaired activation of endothelial nitric oxide synthase and the inhibition of vascular relaxation, leading to hypertension and diastolic heart failure. This work was funded by the SFB 834 and a collaboration with the groups of Ingrid Fleming (Frankfurt) and Ralph Schermuly (Gießen).

Link to article


3rd Jun 2015 - When quality control fails neuropathies develop

Defects in the quality control systems of cells are often fatal. This is seen in particular in neurodegenerative diseases such as Alzheimer's or Parkinson's. As published in today’s online version of Nature, a research team led by Ivan Dikic discovered a new autophagy receptor which plays a central role in cellular quality control. Mutations in this receptor impair its function and cause a hereditary neuropathy named HSAN II. This milestone study not only gives insight into the pathophysiology of a disastrous disease, but also emphasizes the importance of the autophagy network for the wellbeing of cells. Link to German press release, English press release, original article.

Link to Press Release English, German
Link to original article on Nature
Link to News & Views on Nature



2nd Jun 2015 - Amino acid dependent mTORC1 regulation by SLC38A9

The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues such as nutrient status and energy level. Amino acids induce mTORC1 activation on lysosomes via the small Rag GTPases and the Ragulator complex, thereby controlling protein translation and cell growth. As reported in Molecular and Cellular Biology the group of Dr. Christian Behrends identified the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex on lysosomes. Briefly, SLC38A9 regulates mTORC1 activity in an amino acid and RHEB GTPase dependent manner by defining the intracellular localization of mTOR. Based on these findings, the Behrends lab proposes a new mechanism by which amino acids control mTORC1.

Link to article in Molecular and Cellular Biology


12th May 2015 - Novel gene causing Amyotrophic lateral sclerosis

ALS (Amyotrophic lateral sclerosis ) is a devastating disease characterized by loss of motor neurons and neurodegeneration, usually leading to death within 3-4 years. Despite being classified as rare disease, public awareness is very high, fueled by celebrity patients like Stephen Hawking and culminating in last years’ Ice Bucket Challenge, the first charity campaign with global impact. Still, there is no treatment for ALS, despite intensive research in the field.
Researchers from IBC2 and BMLS have now made a major step to a better understanding of the genes causing ALS. They were part of an international research team initiated by Ulm and Umea Universities, which discovered that mutations in a particular kinase (Tank-binding kinase 1, TBK1) lead to loss of function of this important regulator in families with a history of ALS. The Frankfurt team around Ivan Dikic was particularly involved in revealing the functional role of TBK1 in ALS, showing that the mutations found in patients disrupt the interaction of TBK1 with its adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis as well as in bacterial infection defense. Co-lead author Benjamin Richter from the Dikic lab comments: “For me as a medical doctor working in basic science this story represents the ideal case of explaining the pathophysiology of a disease by a collaborative effort across disciplines.” The exiting results are published in the latest issue of Nature Neuroscience and are put in perspective in an accompanying News and Views article.

Link to the artikel on Nature Neuroscience
Link to News and Views


9th April 2015 - CEF Focus Project awarded to team of junior research group leaders

The CEF Macromolecular Complexes approved funding for the proposal of Masato Akutsu, Christian Behrends, Vladimir Rogov and Volker Dötsch on the spatio-temporal regulation of protein complexes by the family of human ATG8 proteins. By employing highly complementary structural, biophysical, biochemical and cell biological approaches this young team of researchers seeks to understand the role of the ubiquitin-like ATG8 proteins as reversible, membrane-bound scaffolds that help organizing protein and protein complexes spatially to control cellular pathways other than autophagy. The research program is supported with 300.000 Euro for two years starting June 2015.

Link to CEF Macromolecular Complexes


12th Feb 2015 - Role of GABARAP proteins as signaling scaffolds in TIAM1-RAC1 signaling

Spatio-temporal control is critical for RAC1 signaling. In this week’s online issue of Molecular Cell the group of Dr. Christian Behrends report the identification of CUL3-KBTBD6/KBTBD7 as ubiquitin ligase that locally regulates the abundance of the guanine exchange factor TIAM1. Furthermore, membrane targeting of CUL3-KBTBD6/KBTBD7 is mediated by GABARAP proteins, thereby establishing functions of this subfamily of human ATG8 proteins beyond autophagy and membrane trafficking.

For the full article click here


5th Jan 2015 - Fritz Thyssen Foundation supports autophagy research

Alexandra Stolz V Alexandra Stolz, postdoctoral researcher at IBCII, received a grant from the Fritz Thyssen Foundation to fund her proposed project on targeting the autophagy system. The research program is supported with 150.000 Euro over the next two years.
The Fritz Thyssen Foundation is an active supporter of basic science since more than 50 years, focusing especially on support for junior researchers.

Link to The Fritz Thyssen Foundation



6th Jan 2015 - PLEKHM1: A Multifunctional Adaptor for the Endolysosomal System

As reported in this month’s issue of Molecular Cell and Cell Host & Microbe, an international team of researchers led by Prof. Ivan Dikic has shed light on the molecular function of the protein PLEKHM1, that has previously been shown to regulate bone density in humans and rats. The team has identified two novel functions for the protein that are important for human disease; firstly, facilitating the removal of toxic protein aggregates and preventing their accumulation, which is relevant for diseases such as Parkinson’s. Secondly, controlling the intracellular growth of invading pathogens such as Salmonella. Both studies provide insight into the molecular mechanisms of cellular processes with high relevance to human diseases, and give rise to potential targets for therapeutic intervention.

Preview for Molecular cell article here
Molecular cell article here
Cell host & Microbe article here


2nd Jan 2015 - Unprecedented insights into proton pumping

Cells convert the energy extracted from foodstuff into ATP, the universal currency of cellular energy. Mitochondrial oxidative phosphorylation is carried out by five large enzyme complexes. The Zickermann group from Institute of Biochemistry 2 together with colleagues from the Cluster of Excellence Macromolecular Complexes in Frankfurt and from Freiburg University solved the 3D structure of mitochondrial complex I, the largest and most complex enzyme of this fundamental metabolic pathway. Complex I comprises more than 40 subunits and has a mass of almost 1 Mega-Dalton. Its major task is to pump protons across the inner mitochondrial membrane, thereby driving ATP synthesis. The exact mechanism, however, has remained elusive. In today?s issue of Science, the Zickermann group now reports new and exciting insights into the structure of this giant enzyme complex, explaining how it transmits the energy needed for proton pumping over quite a long range. The team was able to come up with a new model, by which a sequential formation of charged intermediates causes a concerted rearrangement of structural elements within the enzyme, thereby ultimately triggering proton translocation at the pump sites.

Link to article here


18th Dec 2014 - Lina Herhaus receives an EMBO longterm postdoctoral fellowship

Lina Herhaus V

EMBO will fund her work that is focused on understanding the role of linear ubiquitylation in tumor stromal crosstalk.


29th Sep 2014 - Revealing the cause of early onset liver cancer

A multidisciplinary, international team led by C. Kubisch (Ulm University), K. Ramadan (Oxford University), J. Terzic (Split University), D. Amor (University of Melbourne) and I. Dikic (Goethe University in Frankfurt) reports in today's online issue of Nature Genetics the discovery of a hitherto unknown mutation causing early onset liver cancer. Individuals carrying this mutation are highly likely to develop liver cancer during childhood, and also show multiple signs of premature aging. The mutation disrupts the function of a gene called SPRTN, resulting in accumulation of DNA damage during each cell division and subsequent chromosome instability. Ivan Dikic comments: "This is an excellent example of success of long term projects. It started more than 7 years ago, at the time focusing on Ub-dependent DNA repair pathways. Later, by serendipity, the results turned out to be critical for understanding the development of hepatocarcinoma. The project has attracted several collaborators around the world and only by closely collaborating we were able to successfully accomplish this task. It also shows why a certain stamina on the side of fund providers (7 years without a single publication) is essential for addressing big and important questions in biomedicine."

Link to article here
Link to press release here


25th Aug 2014 - Ivan Dikic to become a Vallee Visiting Professor at Harvard Medical School

Eddy Fischer (Nobel laureate in Medicine 1992) and Ivan Dikic at the Vallee Foundation symposium, Boston, 2014

The Vallee Foundation announced the appointment of six new Vallee Visiting Professors (VVPs), who will receive the resources to spend one month at a premier biomedical research institute of their choice. Besides Ivan Dikic, the award goes to Bonnie Bassler, Chris Dobson, Tyler Jacks, Thomas Shenk and Andreas Strasser this year. Since 1997, 47 VVPs have been appointed, and the program has been a great success in fostering intellectual exchange, building scientific partnerships and kicking off exciting new projects. Ivan Dikic will join Harvard Medical School in 2015 for his VVP sabbatical.

More info on the Vallee Foundation here
For ASBMB PDF click here


5th Aug 2014 - Role for ARAF kinase in MAPK activation and Cell migration

RAF kinases are direct RAS effector proteins and upon activation they trigger the classical MAPK signaling pathway that control various fundamental cellular processes. RAF family comprises of ARAF, BRAF and CRAF of which ARAF remains understudied. In a cover story published this week in Science Signaling, Krishna Rajalingam's group demonstrate an obligatory role for ARAF kinase in mediating MEK1/2-ERK1/2 activation and tumour cell migration in a cell type dependent manner.

For the editors summary of Mooz et al please click here

For the full article click here
For podcast click here


21st Jul 2014 - Krishnaraj Rajalingam wins a Heisenberg Professorship from the DFG

Krishnaraj Rajalingam, a group leader from IBCII and a BIF-PLUS3 fellow got selected for the prestigious W3 Heisenberg professorship in Cell Biology from the DFG. With this award he joins the Forschungszentrum für Immuntherapie (FZI) at the Johannes Gutenberg-Universität Mainz (JGU) to establish a cell biology unit. IBCII director Prof. Ivan Dikic congratulates Krishna on this accomplishment!

For the press release from the Boehringer Ingelheim Foundation click here
For the press release from the university of Mainz click here


10th Jul 2014
Novel role for ubiquitin in the physical and functional disassembly of a MAPK cascade
Mitogen activated protein kinases (MAPKs) are a class of highly conserved family of protein kinases that control fundamental cellular processes like cell survival, migration and differentiation. The group of Krishna Rajalingam from IBCII, now discovers a novel role for ubiquitination in the inactivation of MEKK2/3-MEK5-ERK5 signaling pathway, thus adding another layer of regulation of MAPKs. They identify that two members of the inhibitors of Apoptosis Proteins (IAPs) family, XIAP and cIAP1, directly bind and conjugate a unique type of ubiquitin chains to MEKK2 and MEKK3, which directly impairs the complex formation between MEK5 and ERK5 thus inactivating this signalling pathway. They further identify that XIAP negatively controls human myogenic differentiation by regulating the activation dynamics of ERK5-MAPK cascade. The observations by Takeda AN et al are now published in EMBOJ
For the full article please click here
For the HYS highlight by Klein and Cobb in EMBOJ please click here


12th Jun 2014
SUMO-mediated control of a histone-modifying complex
The group of Stefan Müller unraveled a novel facet of SUMO-regulated gene expression. They discovered that the SUMO-specific isopeptidase SENP3 is needed for proper activity of histone-modifying MLL1/2 complexes. Removal of SUMO2/3 from the MLL1/2 subunit RbBP5 is required for the activation of a subset of HOX genes, including the regulator of osteogenic differentiation DLX3. The importance of this pathway for cell differentiation was demonstrated in a human stem cell model.  The paper by Nayak et al. was published online in Molecular Cell on June, 12.


25th Apr 2014
HFSP Program Grant for IBC2
The International Human Frontier Science Program (HFSP) Organization announced this year's winners of the competition for one of the prestigious HFSP research grants. Amongst the awardees is the Dikic group, who together with the Sidhu group (Canada), the Komatsu group (Japan) and the Sander group (U.S.) will receive 1,35 M USD for the next 3 years. "This award considerably pushes autophagy research in Frankfurt, especially because it funds one of our most innovative projects. Within the next 3 years, we expect to gain a lot of knowledge about molecular targeting of the autophagy network", says Ivan Dikic, IBCII director. Read more


10th Apr 2014
The control of signaling in immunity and inflammation
The groups of Ivan Dikic and Masato Akutsu have moved closer in understanding how a novel form of protein modification, the linear ubiquitination, controls central pathways of immunity and inflammation. In a collaborative effort, they showed that the two enzymes responsible for assembling and disassembling linear ubiquitin chains are contained in one complex. By structural analysis, they managed to decipher the molecular details of the interaction between these two key enzymes and were able to show how the opposing activities of the complex are controlled. Their results are published in the current edition of Molecular Cell online.


2nd Feb 2014
Deciphering the molecular mechanisms behind the cell's power packs
Complex I is the largest enzyme of the respiratory chain, a fundamental metabolic pathway operating to supply the cell with energy. Dysfunction of complex I causes numerous neuromuscular and neurodegenerative diseases in humans. Combining biochemical and structural evidence the Zickermann group now succeeded in shedding light on the essential role of accessory subunit NB4M (NDUFA6/LYRM6) for complex I function. The results are published in the current early edition of the journal PNAS (Angerer et al., doi: 10.1073/pnas.1322438111).
Read more


24th Jan 2014
IBC2 and BMLS appointing two new group leaders
In a joint effort, IBC 2 and the Buchmann Institute (BMLS) recruited two new group leaders: Dr Anja Bremm (left) who received a prestigious Emmy Noether Fellowship from the German Research Foundation (DFG) and Dr Masato Akutsu (right) who will be heading a group endowed by the Leibniz Prize awarded to Ivan Dikic by the DFG. Both groups will be located in the BMLS on Riedberg campus, Anja Bremm mainly concentrating on cellular signaling, and Masato Akutsu strengthening the structural biology platform.
Link to BMLS Website


22th Nov 2013 - Structure of HOIP catalytic core solved.
In collaboration with Katrin Rittinger at the MRC-NIMR in London, the Dikic group solved another molecular puzzle about the formation of specific Ubiquitin chains. In the current issue of Nature, they report the crystal structure of the catalytic core of HOIP, the critical enzymes involved in forming linear (Met1-linked) Ubiquitin chains. These chains are important regulators of cellular signalling, and knowing the molecular structure of the complexes involved is an important step forward to understanding how these pathways control innate immunity and inflammation.
Link to nature publication


19th Nov 2013 - Who's most cited of them all?
In its recent issue, Laborjournal (LJ) publishes a citation analysis in the field of cell biology covering the period from 2007 to 2010. Instead of asking the mirror, LJ searched the database "Web of Science" for authors based in Germany, Austria and Switzerland. Amongst the Top 5: IBC2 director Ivan Dikic with 1886 citations of 35 articles. One article from the Dikic lab made it under the Top 10 of most cited articles: the report about a role for the protein NBR1 in autophagy , published by Kirkin and collaborators 2009 in the journal Molecular Cell.
Link to article in Laborjournal
Link to Kirkin et al paper


30th Oct 2013
Bless the team work
It took years to develop, and the input of scientists from five countries: BLESS, a novel technology for mapping DNA breaks by next generation sequencing. The resulting publication in Nature Methods by Crosetto, Dikic, Rowicka, and many colleagues is now featured by Laborjournal.
Link to LJ article in German
Link to original artcle
Link to BLESS website


22th Oct 2013 - LOEWE program Ub-Net recruitment drive
The LOEWE program Ubiquitin-Networks is a newly established interdisciplinary research network at the Goethe University which is led by Ivan Dikic.
The network recently received funding and is looking to recruit 1 Junior Group Leader, 1 Postdoc, and 12 PhD students. Deadline for applications is 7th November. Read full advertisement


16th Oct 2013 - New Group Leader
The IBCII welcomes Dr. Andreas Ernst from University of Toronto as independent group leader.
The research of his newly established protein engineering group is focussed on generating intracellular tools to study various signaling pathways.


Read more about Andreas Ernst

25th Aug 2013 - Award-winning cancer reseacher from Croatia

Read the full article here
Read more about Ivan Dikic


Ivan Dikic V 8th Jan 2013 - Professor Ivan Dikic receives Ernst Jung Prize for medicine

8th January 2013. The Jung Foundation for Science and Research announced that Frankfurt professor Ivan Dikic will receive the Ernst Jung Prize 2013 for his groundbreaking work in understanding the role of Ubiquitin in cellular signal regulation. The prize is awarded with 150,000 euro and will be presented at a ceremony on 3rd May in Hamburg.

Press Release
Read more about Ivan Dikic


6th Dec 2012 - Leibniz Prize 2013 for Frankfurt professor Ivan Dikic.

In recognition of his groundbreaking work in decrypting the Ubiquitin code, Ivan Dikic is to receive the Gottfried Wilhelm Leibniz Prize 2013, Germany's most prestigious scientific award. The award is funded and presented by the German Research Foundation (DFG). It is the research prize with the highest endowment worldwide and comes with a grant of 2.5 M Euro.

Press Release
Read more about Ivan Dikic
Ivan Dikic in DFG


16th Oct 2012 - Dr.Krishnaraj Rajalingam, an Emmy Noether Fellow from IBCII has been selected to be a PLUS3fellow of the Boehringer Ingelheim Foundation.

BIF will fund his research on Inhibitors of Apoptosis (IAPs) with a generous support of 825000 euros for the next three years.

Press Release
Read more about Krishnaraj Rajalingam


1st August 2012 - 2013 ASBMB William C. Rose Award goes to BMLS Director Ivan Dikic.

The Award honors the pioneering work of Ivan Dikic in understanding the Ubiquitin code, and his efforts in training and education of young scientists.

Press Release
Read more about Ivan Dikic
Online link:


18th June 2012 - Seeing Ubiquitin chains in cells.

An international team of scientists led by IBCII director Ivan Dikic developed specific Ubiquitin biosensors for in vivo application. This approach might mark a major technical breakthrough in detection of Ubiquitin signals in living cells. It is published in today's online issue of Molecular Cell.

Link to full article
PDF Link
Read more about Molecular Signaling Group


10th May 2012 - A novel mechanism regulating SUMO-dependent protein networks.

The covalent attachment of the ubiquitin-like modifier SUMO to proteins serves an important mechanism for the control of protein-protein interactions. This is generally mediated via recognition of a SUMO-conjugate by an interaction partner that contains a specific SUMO interaction module, termed SIM (SUMO interaction motif). A major question is how the dynamics of SUMO/SIM interactions are regulated. Recent work done by Rebecca Ullmann in Stefan Muller's group together with co-workers from the Lombardi Cancer Center in Washington now uncovered an acetyl-dependent switch that determines the selectivity and dynamics of SUMO-SIM interactions (Molecular Cell, online May 10, 2012). In this context they show that acetylation of SUMO within a basic interface prevents binding to SIMs in PML, Daxx, and PIAS. One the other hand, acetyl-SUMO specifically binds to the Bromodomain of the co-activator p300. This acetyl-dependent switch of SUMO-mediated protein interactions attenuates SUMO-regulated gene silencing and affects the assembly of PML nuclear bodies. This work thus unravels a novel interplay of post-translational modifications that expands the regulatory repertoire of SUMO signaling.
Original Article:
Ullmann R, Chien C D, Avantaggiati M L, Muller S (2012) An acetylation switch regulates SUMO-dependent protein interaction networks, Mol Cell, online May 10, 2012, DOI 10.1016/j.molcel.2012.04.006

Read more about SUMO Signaling Group


23th January 2012 - Novel mechanism regulating cell shape and migration unveiled.
Cell shape and migration are controlled by RhoGTPases, a family of small GTPases whose activation is controlled by nucleotide binding. Rac1 is an important member of this family and

studies from the Cell death Signalling group from IBCII has shed light into ubiquitin dependent inactivation of Rac1 signalling. New results just published in EMBOJ revealed an evolutionarily conserved role of Inhibitors of Apoptosis (IAPs) in directly regulating the ubiquitylation and degradation of Rac1. Thus loss of IAPs changes the shape and mode of migration in normal and tumour cells. IAPs also regulate the development of cerebellum during zebrafish development in a Rac1 dependent manner.

Read the full article

Read the HYS highlight
Read the research highlight from Nat. Rev. Mol. Cell Bio.
Read the faculty of 1000 evaluation
Read more about Krishna Rajalingam


24th October 2011 - Interview with Prof. Dr. Dr. Ivan Dikic, director of the Frankfurt Institute of Molecular Life Sciences (FMLS)
If you were granted one wish for the advancement of your research projects, what would this be?
Well, I've always valued and emphasized a creative atmosphere. It not only means being surrounded by intelligent people, but also having enough time

to think. Not having countless administrative duties, committees, applying for funding, etc. Scientists need time to develop brilliant ideas that help address issues we normally would not have time to consider. So my wish would be that we scientists do not have to waste too much valuable time on administrative issues, but can dedicate ourselves to conducting research.

Read whole story here

Read more about Ivan Dikic


13th September 2011 - ERC Starting Grant awarded to Dr. Christian Behrends:
The ERC approved funding for his proposal on Xenophagy and bacterial avoidance (XABA). Briefly, microbial pathogens that successfully parasitize eukaryotic cells have evolved to evade autophagic microbial defenses (xenophagy) and subvert the host autophagic responses for their own survival and/or growth.

Central to xenophagy is cargo recognition and dynamic rearrangements of membrane-bound compartments to sequester and deliver pathogen load for lysosomal degradation. Microbial adaptation strategies identified to date have targeted both of these crucial and intertwining functions. However, the precise molecular mechanisms underpinning pathogen avoidance of host-cell autophagy and immune responses as well as their potential roles in microbial pathogenesis are only rudimentarily understood. The XABA project is funded with 1.600.000 Euro for five years starting January 2012.

Whole story in Press release
More about Christian Behrends


26th May 2011 -New defense mechanism against Salmonella elucidated.

Iinfection with Salmonella, epithelial cells can get rid of the unwanted invader by a process called autophagy. In today's issue of the journal Science, an international group of scientists around IBC2 director Ivan Dikic describes how selectivity is achieved in this process.

Read full article or in Press release

19th April 2011
A new Emmy Noether Fellow at the IBCII: Dr. Christian Behrends received the prestigious Emmy Noether Research Fellowship by the DFG. His independent group will be funded for three years with a perspective two3 years extension. The mammalian

autophagy signaling pathway is at the center of Dr. Behrends's research activities. In particular, he is interested in the dynamics of the autophagy interaction network under different physiological conditions

More about Christian Behrends
Whole story in Press release


31st March 2011 - A step towards understanding chronic dermatitis: An international team of scientists led by IBCII director Ivan Dikic discovered a novel role for the protein SHARPIN in immune signalling.

In today's issue of Nature, they show how SHARPIN stimulates formation of linearized ubiquitin chains, triggering activation of a central regulator of immune responses.

Read full article


1st Feb 2011 - IBCII is pleased to announce its new W2: Prof. Stefan Müller is appointed W2 professor in biochemistry at IBCII and will be an independant group leader for SUMO signaling group.

More about Stefan Müller


1st Nov. 2010 - New group leader
Dr. Christian Behrends from Harvard Medical School in Boston will join IBCII as an independant group leader. He will establish the Autophagy signaling group.

More about Christian Behrends