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New class of peptide from bacteria is a potential insecticide
FRANKFURT. Nature often produces a whole weaponry of active ingredients to ensure it is well prepared for any scenario that might occur. Pharmacists and medical experts have meanwhile learnt from this, since pathogens develop resistance more easily to single active drugs than to a combination therapy. The research group led by Professor Helge Bode has now discovered a whole class of new peptides with which bacteria are able to kill insect larvae.
The peptides, known as rhabdopeptide/xenortide peptides (RXPs), are produced exclusively by the bacterial genera Photorhabdus and Xenorhabdus. They live in symbiosis with nematodes, together with which they infect and kill insect larvae. Since many RXPs are toxic for eukaryotic cells (including insect cells) and are produced by many different strains of Xenorhabdus and Photorhabdus, they presumably play a very important role during infection.
One single strain of bacteria can produce up to 40 RXP derivates. As the research group, which is led by Professor Helge B. Bode, Merck Endowed Professor of Molecular Biotechnology at Goethe University Frankfurt, reported in the latest issue of Nature Chemistry, it was surprising to see that only a maximum of four enzymes is required for their production. Bode compares them with classic chemical catalysts for the formation of polymer chains. His group has successfully solved the mechanisms responsible for the production of the unusually high diversity of RXPs.
Why do the bacteria produce a whole library of RXPs instead of single compounds? The researchers explain that the bacteria cannot control into which insect larvae they are delivered by their nematode host. However, in order to survive they must be able to kill any insect quickly and efficiently and direct the mixture of substances at perhaps completely different target sites in the insect cells at the same time. “Imagine shooting with a shotgun”, explains Bode, “even if you’re a poor marksman, there’s a good chance that the spray of bullets will ensure that at least one hits the target!”
Future work will focus on detecting the exact mode of action of the RXPs and identifying, by means of structure-activity analysis, particularly potent derivates, which can then be produced biotechnologically or chemically and perhaps used as insecticides.
Xiaofeng Cai, Sarah Nowak, Frank Wesche, Iris Bischoff, Marcel Kaiser, Robert Fürst and Helge. B. Bode: Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design, in: Nature Chemistry, DOI: 10.1038/NCHEM.2671
A picture can be downloaded from: http://www.uni-frankfurt.de/64290802
Further information: Prof. Dr. Helge Bode, Merck Endowed Professor of Molecular Biotechnology, Tel.: +49(0)69-798-29557, H.Bode@bio.uni-frankfurt.de.
Atomic physicists in Frankfurt measure bond length/precise testing of quantum-mechanical tunnel effect
FRANKFURT. Helium atoms are loners. Only if they are cooled down to an extremely low temperature do they form a very weakly bound molecule. In so doing, they can keep a tremendous distance from each other thanks to the quantum-mechanical tunnel effect. As atomic physicists in Frankfurt have now been able to confirm, over 75 percent of the time they are so far apart that their bond can be explained only by the quantum-mechanical tunnel effect.
The binding energy in the helium molecule amounts to only about a billionth of the binding energy in everyday molecules such as oxygen or nitrogen. In addition, the molecule is so huge that small viruses or soot particles could fly between the atoms. This is due, physicists explain, to the quantum-mechanical “tunnel effect”. They use a potential well to illustrate the bond in a conventional molecule. The atoms cannot move further away from each other than the “walls” of this well. However, in quantum mechanics the atoms can tunnel into the walls. “It’s as if two people each dig a tunnel on their own side with no exit”, explains Professor Reinhard Dörner of the Institute of Nuclear Physics at Goethe University Frankfurt.
Dörner’s research group has produced this helium molecule in the laboratory and studied it with the help of the COLTRIMS reaction microscope developed at the University. The researchers were able to determine the strength of the bond with a level of precision not previously achieved and measured the distance between the two atoms in the molecule. “The helium molecule is something of a touchstone for quantum-mechanical theories, as the value of the binding energy theoretically predicted is heavily dependent on how accurately all physical and quantum-mechanical effects were taken into account”, explains Dörner.
Even the theory of relativity, which is otherwise mainly required for astronomical calculations, had to be incorporated here. “If even just a small mistake occurs, the calculations produce major deviations or even indicate that a helium molecule cannot exist at all”, says Dörner. The precision measurements performed by his research group will serve as a benchmark for future experiments.
Two years spent taking measurements in the cellar
Dörner’s research group began investigating the helium molecule back in 2009, when the German Research Foundation awarded him a Reinhart Koselleck Project and funding to the tune of € 1.25 million. “This type of funding is risk capital, as it were, with which the German Research Foundation supports experiments with a long lead time”, explains Dörner. He was thus able to design and set up the first experiments with his group. Initial results were achieved by Dr. Jörg Voigtsberger in the framework of his doctoral dissertation. “In the search for atoms which ‘live in the tunnel’, Jörg Voigtsberger spent two years of his life in the cellar”, recalls Dr. Till Jahnke, senior lecturer and Voigtberger’s supervisor at the time. It is there, in the cellar, that the laser laboratory of the atomic physics group is housed.
Stefan Zeller, the next doctoral researcher, considerably improved the equipment with the help of Dr. Maksim Kunitski and increased measurement precision still further. To do so, one of his tasks was to shoot at the very weakly bonded helium molecule with FLASH, the free-electron laser at the DESY research centre in Hamburg and the largest "photon canon" in Germany. “Stefan Zeller’s work was remarkable. It was his untiring effort, his excellent experimental research skills and his ability not to be disheartened by temporary setbacks which made our success possible at all”, remarks Professor Dörner, Zeller’s doctoral supervisor.
Already beforehand the results have attracted considerable interest at national and international level. They will now appear in the renowned journal “Proceedings of the National Academy of Sciences of the United States of America (PNAS)” and are also part of the research work for which the group was awarded the Helmholtz Prize 2016.
S. Zeller, M. Kunitski, J. Voigtsberger, A. Kalinin, A. Schottelius, C. Schober, M. Waitz, H. Sann, A. Hartung, T. Bauer, M. Pitzer, F. Trinter, C. Goihl, C. Janke, M. Richter, G. Kastirke, M. Weller, A. Czasch, M. Kitzler, M. Braune, R. E. Grisenti, W. Schöllkopf, L. Ph. H. Schmidt, M. Schöffler, J. B. Williams, T. Jahnke, and R. Dörner:
Imaging the He2 quantum halo state using a free electron laser, in: PNAS, DOI
A caricature can be downloaded from: www.uni-frankfurt.de/64324412
“When two loners are forced to share a bed, they move well beyond its edges to get away from each other.”
Further information: Professor Dr. Reinhard Dörner, Institute of Nuclear Physics, Max-von-Laue-Str. 1, Tel.: +49(0)-798-47003, firstname.lastname@example.org;
PD Dr. Till Jahnke, Institute of Nuclear Physics, Max-von-Laue-Str. 1, Tel.: +49(0)-798-47025, email@example.com
A novel ubiquitination mechanism explains pathogenic effects of Legionella infection
FRANKFURT. The attachment of ubiquitin was long considered as giving the „kiss of death“, labelling superfluous proteins for disposal within a cell. However, by now it has been well established that ubiquitin fulfils numerous additional duties in cellular signal transduction. A team of scientists under the lead of Ivan Dikic, Director of the Institute of Biochemistry II at Goethe University Frankfurt, has now discovered a novel mechanism of ubiquitination, by which Legionella bacteria can seize control over their host cells. Legionella causes deadly pneumonia in immunocompromised patients.
According to the current understanding, the coordinated action of three enzymes is needed for attaching ubiquitin to other proteins. In April this year, U.S. scientists described an ubiquitination reaction that depends only on a single enzyme from Legionella bacteria. The Dikic team together with the group of Ivan Matic (Max Planck Institute for Biology of Ageing, Cologne, Germany) now elucidated the underlying molecular mechanism of its action and revealed a hitherto unknown type of chemical linkage between ubiquitin and target proteins.
Their discovery breaks new ground in the field. Sagar Bhogaraju, researcher in the Dikic laboratory, comments: “Most exciting is of course the question if this unusual ubiquitination also occurs in human cells independently of bacterial infection and if there are similar, so far unknown enzymes in humans, which may have a profound influence on cellular processes.”
When studying the new mechanism in more detail, the Frankfurt scientists were very surprised to find that the Legionella enzyme does not only transfer ubiquitin onto target proteins, but also chemically manipulates the remaining pool of ubiquitin molecules. Modified ubiquitin almost completely inhibits the conventional ubiquitination system, thereby revealing a new role for this enzyme during Legionella infections.
Several important cellular processes are affected by this shut-down of the ubiquitination system, which can also cause a rapid cell death. The Dikic team showed for example that modified ubiquitin prevents degradation of mitochondria (a process called mitophagy), affects transduction of inflammatory signals and constrains protein degradation.
“Most likely, Legionella is not the only bacterium using this mechanism. We hope that our results help to identify new strategies for the development of antibacterial agents, which could complement conventional antibiotics by limiting cellular damage induced by bacterial enzymes”, explains Dikic the high medical relevance of their discovery.
The group of Ivan Dikic is located at both the Institute of Biochemistry II and the Buchmann Institute for Molecular Life Sciences at Goethe University Frankfurt and has previously contributed significantly to a paradigm change in the ubiquitin field. Ivan hypothesized early on that ubiquitin signals are recognized and translated by specialized domains in other proteins. He identified ubiquitin-binding domains in more than 200 ubiquitin receptors and was able to prove their role in diseases like cancer, amyotrophic lateral sclerosis and Parkinson’s.
Publication: Bhogaraju S, Kalayil S, Liu Y, Bonn F, Colby T, Matic I, Dikic I. Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination. Cell. 2016 Dec;167(6). DOI10.1016/j.cell.2016.11.019
Information: Dr. Kerstin Koch, Institute of Biochemistry II, University Hospital Frankfurt, Phone: +49 69 6301 84250, firstname.lastname@example.org
Study by PwC and Goethe University Frankfurt reveals: In Dax and MDax-listed companies, bonuses are decoupled from corporate success after payout
Frankfurt. To date, the bonuses paid out to executive board members in Germany have not been sufficiently linked to long-term corporate success. This is the conclusion reached in the new “Remuneration Report” by consultants PwC in cooperation with Goethe University Frankfurt. Whilst about 60 percent of overall remuneration for Dax and MDax board members is indeed made up of performance-related payments – of which in turn more than half are long-term – most of these payments, which are known as Long Term Incentives (LTIs), are in cash rather than based on share plans. That means: Bonuses are automatically decoupled from business development the moment they are paid out.
“When compared at international level, Germany can thus be classed as a special case. In our view, it would be more advantageous if long-term bonuses were awarded in the shape of shares in the respective company and the board members were also bound by means of corresponding clauses actually to keep these securities for a longer period of time, if necessary even beyond their term of office. This would ensure that it is in board members’ vested interest really to work towards the company’s long-term success”, says Remo Schmid, co-author of the report and partner at PwC in Germany responsible for remuneration issues.
CEOs earn almost twice as much as their board colleagues
For the report, PwC and Goethe University Frankfurt examined remuneration structures in Dax and MDax companies. The analysis shows that developments in executive board remuneration in 2015 differed in comparison to the previous year: On average, a Dax CEO earned € 5.6 million, a plus of a good 3 percent. Other board members earned € 2.9 million, which equates to a minus of 2 percent. CEOs in MDax companies earned € 2.5 million on average, whilst their board colleagues were paid € 1.3 million. In other words: On the Dax, the barometer for blue chip companies, top managers are paid more than twice as much as their counterparts in medium-sized enterprises on the MDax. What’s more: The average CEO earns on average almost double the salary of a “normal” board member.
Women are still greatly underrepresented
According to the analysis, the percentage of women amongst top-level executives is rising at an astoundingly slow pace. At the end of 2015, a good 91 percent of all board positions in Dax companies were still occupied by men – whilst in MDax firms it was even 96 percent. The picture is far better, though still not good, in regulatory bodies: In Dax companies, 26 percent of all supervisory board members were female compared to 18 percent in MDax firms. “In many enterprises, cultural change in this respect would be highly desirable”, says Professor Dr. Hans-Joachim Böcking, co-author of the report and professor at Goethe University Frankfurt. Still: “At least as far as the basic salary of executive and supervisory board members is concerned, no gender-specific differences were detected either in Dax or MDax companies”, says Böcking.
A chairman on the supervisory board of a Dax company received an average total remuneration in 2015 of € 311,000. Deputies earned € 230,000, other supervisory board members € 127,500. Pay scales in MDax firms were far lower. Here companies considered their main overseer to be worth an average of € 183,500, the deputy was paid € 121,500 and the other members received € 75,000. Worth noting: Whilst the fixed remuneration for supervisory board members increased on average by about 12 percent in Dax and MDax companies, variable remuneration is still on the decline: in 2014, four out of ten Dax companies still made some form of variable payment. In 2015 it was only three out of ten.
In PwC’s view, its task is to build trust in society and solve important problems. 223.468 employees in 157 countries contribute to these goals by providing high-quality, sector-specific auditing, tax and corporate consulting services. The PwC brand name refers to the PwC network and/or one or several of the legally independent member firms. For further information please see: www.pwc.com/structure.
German Research Foundation funds film studies project by early career researchers for the first time
FRANKFURT. The first Research Training Group ever with a focus on film studies will be established in the course of the coming year at Goethe University Frankfurt. This was announced by the German Research Foundation on the 14th of November. In the framework of the RTG with the title “Configurations of Film”, twelve doctoral researchers and two post-docs will examine from 2017 onwards how film culture is changing in the context of advancing digitalisation in various areas.
Contemporary film culture is often referred to as the “post-cinematographic era”. Professor Vinzenz Hediger, scholar and film expert at the University who will also be the RTG’s speaker, remarks: “Film has expanded its reach more and more beyond public screenings in the cinema. With the proliferation of digital platforms, new forms are developing and new patterns of cinematic experience emerge.” At the same time, film serves increasingly as a creative template in theatre, fine arts and music. Hediger says: “As films circulate ever more widely, they affect other art forms and have a growing impact on other areas of life, including interpersonal communication. This increasing presence of filmic images and formats in all areas of life also constitutes a growing societal challenge.”
The “Configurations of Film” RTG of the German Research Foundation wants to take on this challenge by investigating the current transformations of film and their impact on other art forms and areas of life from an interdisciplinary perspective. The RTG combines an emphasis on historical research with systematic and comparative perspectives; in addition, the programme will use digital methods for film analysis and data mining on the internet, with which, for example, the proliferation of new film formats via platforms such as YouTube or Vimeo can be tracked.
The Research Training Group will build on successful cooperation between Goethe University Frankfurt and the German Film Institute (Deutsches Filminstitut), which together run the Masters degree programme in “Film Culture: Archiving, Programming, Presentation”, and profit from links to other cultural institutions in the Rhine-Main region. The RTG also builds on the interdisciplinary Masters degree programme in “Aesthetics”, which is unique to Frankfurt and in which all the disciplines participating in the RTG are also involved.
Twelve doctoral researchers and two post-docs, who can apply for a German Research Foundation scholarship in the framework of the Research Training Group, will start with their research in 2017. They will be supervised and mentored by 15 researchers from six universities: Goethe University Frankfurt, Offenbach University of Art and Design, Johannes Gutenberg University Mainz, the University of Mannheim and Philipps University Marburg. Alongside film studies and media studies, the disciplines involved include theatre studies, philosophy, musicology, literary studies and sociology. The RTG has an international focus and cooperates with the film studies programmes at Yale University (New Haven, USA) and Concordia University (Montreal, Canada). Funding amounts to about € 3.3 million for the first phase from 2017 to 2022.
In the spirit of the “citizen’s university”, the study programme will include a series of public lectures and events, for example at b3, the Biennale of the Moving Image, and at the cinema of the German Film Museum (Deutsches Filmmuseum), in the framework of which the RTG’s themes and research questions will be discussed in public and address a broader audience.
Further information: Professor Dr. Vinzenz Hediger, Department of Drama, Film and Media Studies, Westend Campus, Tel.: +49(0)69-798-32079, Email: email@example.com