Welcome to Institute of Biochemistry II

Institute of Biochemistry II, an environment where scientists are passionate about their research, where creativity and ideas are generators of success and where lab work and education breed new generations of multidisciplinary professionals.
Upcoming events

Seminar in Biochemistry
Lecturer: Tilmann Bürckstümmer
Date: 24.03.2015

Horizon Genomics GmbH Campus Vienna Biocenter Vienna, Austria

: "An efficient pipeline for CRISPR/Cas-mediated genome engineering in haploid human cells"

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Seminar in Biochemistry
Lecturer: Anton Wellstein
Date: 25.03.2015

Georgetown University Medical School, Lombardi Comprehensive Cancer Center, Washington DC, USA.

: "The Hippo pathway in cancer malignant progression"

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IBCII top News

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, 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

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

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: infection 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