Albumin in high doses improves cardiac function and reduces inflammation
FRANKFURT. Decompensated cirrhosis is a chronic disease linked to numerous complications in its final stage. Professor Jonel Trebicka from Goethe University was involved in carrying out a pilot study demonstrating that the long-term administration of albumin in high doses stabilizes the circulatory function of these patients and protects them from sepsis.
“I was spending a research period at the clinic in Barcelona at the time the clinical study Pilot-PRECIOSA was underway and discussed the results in patients with severe sepsis with the researchers on site," says Professor Jonel Trebicka, hepatologist at the Medical Clinic I at Goethe University.
Albumin is a protein that occurs in human blood where it fulfils numerous tasks. Cirrhosis of the liver reduces its levels, so that patients with decompensated cirrhosis, the stage at which serious complications occur, have been treated with albumin before, but only for short periods.
In the Pilot-PRECIOSA study involving 22 European partners, two groups of patients with decompensated cirrhosis were treated with albumin for three months. One group received a low dose, the other a high dose. Patients who received the higher dose exhibited improved cardiac function and a reduction in the concentration of inflammation markers in their blood.
This treatment is being tested on a larger group of patients in the current follow-up study PRECIOSA, in which Professor Trebicka and Assistant Professor Tanya Welzel from the Medical Clinic I are involved.
“This result is enormously important for our work in the recently founded Micro-Predict Consortium, in which we investigate the importance of the intestinal microbiome in liver diseases: now we will look for microbiome markers that signal a responsiveness to albumin, so that we can apply the therapy more precisely in the future."
In the MICROB-PREDICT project, specialised doctors work together with leading experts in microbiome and medical technology, and the patient organisations ELPA and the Home of Hepatology (EASL). The supporting organization is the European Foundation for the Study of Chronic Liver Failure (EFCLIF), which also sponsored the Pilot-PRECIOSA study. EFCLIF is a foundation connecting a network of more than 100 university hospitals across Europe within EASL, including the University Hospital at Goethe University.
Publication: Fernandez J et al.: Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patient with Decompensated Cirrhosis, in: Gastroenterology (2019), doi: https://doi.org/10.1053/j.gastro.2019.03.021
An image may be downloaded at: http://www.uni-frankfurt.de/77108559
Caption: The Project Microb-Predict directed by Professor Jonel Trebicka will look for albumin markers in intestinal microbiome for a more precise albumin treatment for decompensated cirrhose in the future.
Further information: Professor Jonel Trebicka, Medical Clinic I, Faculty of Medicine, Niederrad Campus, Telefon: +49 178 531 8838, email@example.com
Goethe University secures three ERC Advanced Grants / A total of € 7.7 million for five years
FRANKFURT. Three ERC Advanced Investigator Grants from the European Research Council, amounting to € 7.7 million in total, will go to researchers at Goethe University in Frankfurt. The sociologist Professor Markus Gangl examines whether economic inequality poses a threat to liberal society. The economist Professor Bernd Skiere researches the economic dimensions of cookies, and Helge Bode, Professor for Molecular Biotechnology, aims to discover new drugs based on natural products.
“For the first time, Goethe University has succeed in securing three ERC projects simultaneously in one round of applications. It's a very special challenge for us, and I am delighted," commented University President Professor Birgitte Wolff regarding the announcement of the award winners. “The development of synthetic drugs from natural substances, researching economic mechanisms in the Internet and the scientific examination of the connection between social inequality and societal stability – with their projects, our scientists are investigating important issues of our day," says Wolff.
SYNPEP" Project reprograms natural peptides as drugs
Many clinically used drugs are peptides, which are often produced by microorganisms such as bacteria or fungi. They include important antibiotics such as vancomycin, daptomycin and penicillin, immune suppressors such as cyclosporine, and anti-cancer drugs such as bleomycin. To alter these peptides, the enzymes producing them have to be reprogrammed. This also allows the production of non-natural peptides which do not occur in nature and which might have beneficial or superior properties compared to the original peptide. This is the goal of SYNPEP (Synthetic biology of non-ribosomal peptide synthetases to generate new peptides), headed by Helge B. Bode, Professor for Molecular Biotechnology at the Faculty of Biological Sciences at Goethe University. The project will be funded for five years with € 3.16 million.
Helge Bode came to Goethe University in 2008 when he was appointed Merck Endowed Chair for Molecular Biotechnology. He works on all aspects of microbial natural products, with particular focus on the natural function of these molecules. His group studied this within the framework of an ERC Starting Grant from 2013 through 2018. His second emphasis is on the manipulation of non-ribosomal peptide synthetases, which are the focus of the ERC Advanced Grant just awarded.
“POLAR" Project focuses on social inequality
Professor Markus Gangl was awarded an Advanced Grant for the research project POLAR (Polarization and its discontents: does rising economic inequality undermine the foundations of liberal societies?). The project is dedicated to the issue of whether increasing economic inequality contributes to the undermining of important pillars of Western-liberal society. Professor Gangl and his project team will use survey data from approximately 30 countries in an empirical study of the relationship between growing inequality and social mobility, social cohesion, and the acceptance of democratic values and institutions. The project will be funded with approximately € 2.5 million.
Markus Gangl has been at Goethe University since 2011 as a Professor of Sociology in the area of social stratification and social policy; he also is an Honorary Fellow at the Department of Sociology of the University of Wisconsin-Madison, USA. Before joining Goethe University he held professorships at the University of Wisconsin-Madison and at the University of Mannheim. Professor Gangl is an elected member of the Lepoldina (German National Academy of Sciences), an elected member of the Board of the Research Committee 28 (Social stratification and mobility) of the International Sociological Association, and the Editor-in-Chief of the European Sociological Review, the most important European journal in his field. He currently directs the CORRODE project, also funded by the European Research Council (ERC), which empirically investigates the socio-economic consequences of the financial crisis.
“COOKIES" project researches the value of cookies for advertisers
Cookies allow companies to collect information about users in the Internet. This information is often used to improve the performance of online advertising, which website publishers rely on in order to finance the “free" content to which their users have become accustomed. Yet, the collection of information leads to a loss of privacy. Accordingly, EU policy makers have put forward initiatives to restrict cookie usage (e.g., General Data Protection Regulation (GDPR), upcoming ePrivacy Regulation).
So far, there exists very little empirical knowledge on the trade-off between user privacy and the economic value that website publishers, advertisers, and even users derive from cookies. As a result, policy makers have no way of telling whether their restrictions on cookies have the intended positive consequences for user privacy, or whether any benefits are outweighed by negative effects on the profits of companies—which policy makers also seek to nurture. The research project COOKIES (Economic Consequences of Restrictions on the Usage of Cookies) by Professor Bernd Skiera aims to close this gap. In the project, several data sets will be analysed, including a cookie dataset containing prices for online advertisements from more than 2.8 billion (anonymous) cookies, and an implementation dataset that shows how thousands of websites implemented the EU General Data Protection Regulation that went into effect in 2018. The funding for this project amounts to almost € 2 million.
Bernd Skiera has been Chair for Electronic Commerce at Goethe University since 1999. In Handelsblatt's 2014 ranking, he was named the highest performing research professor in business economics in Germany, Austria and Switzerland. Thirteen of his former doctoral students are now professors in Germany, Austria, the USA, England and Spain; nine are in tenured positions.
Pictures may be downloaded here: http://www.uni-frankfurt.de/77056325
Further information: Prof. Dr. Helge B. Bode, Institute for Molecular Biosciences, Faculty of Biological Sciences, Riedberg Campus, Tel. +49 69 789-29557, H.Bode@bio.uni-frankfurt.de; Prof. Dr. Markus Gangl. Institute for Sociology, Faculty of Social Sciences, Westend Campus, Tel. + 49 69 798-36633, E-Mail firstname.lastname@example.org; Prof. Dr. Bernd Skiera, Chair for Electronic Commerce, Faculty of Business and Econimics, Westend Campus, Tel. +49 69 798-34649, E-Mail email@example.com; Homepage: https://www.marketing.uni-frankfurt.de/professoren/skiera/prof-dr-bernd-skiera.html.
Researchers decode mechanism for diversifying bioactive phenazines
FRANKFURT. Bacteria produce a cocktail of various bioactive natural products in order to survive in hostile environments with competing (micro)organisms. In the current issue of Nature Chemical Biology, researchers at Goethe University demonstrate that they do so by modifying basic structures, similar to the approach taken in pharmaceutical research.
Phenazines are widespread and chemically diverse bacterial natural products that can fulfil various biological functions. Like antibiotics, some derivatives kill bacteria; others are toxic to fungi and/or cancer cells. There are also derivatives that allow the bacteria to survive in an environment that is hostile to them, such as the human body. These virulence factors are often crucial for the bacteria to become pathogenic.
Biochemically, all phenazines are derived from simple basic structures, such as the phenazine-1,6-dicarboxylic acid or phenazine-1-carboxylic acid, whose biosynthesis is well understood. However, these initial structures can be drastically modified in the periphery so that a large number of phenazine derivatives are possible, several of which can indeed be found in different bacteria. The Molecular Biotechnology research group led by Professor Helge Bode has now succeeded in identifying new mechanisms that allow the bacteria to modify these simple basic structures, resulting in derivatives that act on both Gram-positive and Gram-negative bacteria, as well as on cells of higher organisms.
“Bacteria are able to determine which derivatives should be created using a central new aldehyde intermediate as well as the activation of a second biosynthetic gene cluster," explains Dr. Yi-Ming Shi, who investigated this system during a Humboldt scholarship. This means that bacteria use mechanisms for drug development similar to those used in pharmaceutical research, where new derivatives are produced using the same basic structures. Most likely the bacteria use the phenazines to kill other bacteria and fungi that are food competitors in their particular ecosystem. Using a strategy of creating many different kinds of derivatives, the bacteria are well equipped to counteract unknown competitors, as the cocktail of derivatives exhibits a wide range of biological activity.
“It would now be fascinating to find out how bacteria actually recognise which derivatives are required at a given time," states Helge Bode. “Either they produce only those derivatives that are actually required, or the bacteria keep an arsenal of derivatives so that they are prepared for any situation."
The group will therefore continue their research in this area. First results on the underlying regulation mechanisms that could also be used for biotechnical applications appear promising.
Publication: Yi-Ming Shi, Alexander O. Brachmann, Margaretha Westphalen, Nick Neubacher, Nicholas J. Tobias, Helge B. Bode, Dual phenazine gene clusters enable diversification during biosynthesis. Nature Chemical Biology, 2019, 10.1038/s41589-019-0246-1.
A picture may be downloaded at: http://www.uni-frankfurt.de/76883939
Caption: Examples of the phenazine cocktail produced by Xenorhabdus szentirmaii bacteria. Phenazines are not only bioactive, but also exhibit the colours depicted here. Credit: Dr. Yi-Ming Shi
Further information: Professor Helge B. Bode, Molecular Biotechnology, Faculty 15, Riedberg Campus, Tel.: +49 69 798-29557, firstname.lastname@example.org.
Innovative methods lead to foundation of start-up Vivlion GmbH
FRANKFURT. CRISPR/Cas enables the targeted deactivation of genes by cutting DNA at pre-determined sites. This is accomplished by providing the Cas enzyme with a genetic zip code. Using an entire library of zip codes, it is then possible to simultaneously probe multiple sites within the genome, for example to determine which genes are essential for cancer cell survival. This could revolutionize drug discovery.
Unfortunately, however, creation of libraries containing high numbers of zip codes covering the entire genome proved to be difficult. Researchers at Goethe University now succeeded in solving this problem. As Dr Manual Kaulich reports in the scientific journal “eLife", he and colleagues found a reliable method for creating libraries of any magnitude. “Using our newly developed 3Cs technology, we for the first time came up with a library that allows us to investigate the entire genome simultaneously – including non-coding regions outside of genes. In total, our library contains 16.5 million unique zip codes," explains Kaulich, who leads an independent research group at the Institute of Biochemistry II.
The non-coding regions which represent 98% of our genome are of particular interest as they are suspected to hold the key to numerous regulatory mechanisms. CRISPR/Cas reagents produced by the novel method can for example help to better understand mechanisms underlying chemotherapy resistance.
The flash of inspiration hit Manuel Kaulich together with colleague Dr Andreas Ernst, who at that time was also heading a research group at Institute of Biochemistry II. “We were chatting about our different areas of expertise and suddenly there was this compelling idea on how to elegantly combine the two," state Kaulich and Ernst.
Since then, Manuel Kaulich has established numerous additional collaborations, like the one with Dr Anja Bremm, also a group leader at the Institute of Biochemistry II, on the biological relevance of a certain protein class. Together with Institute Director Professor Ivan Dikic, he set up the “Frankfurt CRISPR/Cas Screening Center" (FCSC), which aims at making the technology broadly accessible for studying unknown cellular functions. Ivan Dikic comments: “This exciting discovery is also attributed to the unique culture of our Institute, which inspires creativity, new ideas, and teamwork."
Through its technology transfer subsidiary Innovectis, Goethe University has meanwhile applied for a patent to protect the innovative idea. The patent also forms the basis for the start-up company Vivlion GmbH, which was recently founded by three employees of the Institute of Biochemistry II together with Goethe University. Vice President Professor Manfred Schubert-Zsilavecz comments: “This is a milestone for the Goethe University: Vivlion is the first start-up that was founded with the participation of Goethe University employees."
Innovectis prepared the grounds for the start-up to take off. As Innovectis CEO Martin Raditsch states, “I am very happy about successfully starting Vivlion GmbH from out of Goethe University, because we have here a very promising technology coming together with an excellent working group and a perfectly assembled founding team." The company will introduce the first 3Cs reagents to the market in the upcoming months.
Publication: Wegner M, Diehl V, Bittl V, de Bruyn R, Wiechmann S, Matthes Y, Hebel M, Hayes MG, Schaubeck S, Benner C, Heinz S, Bremm A, Dikic I, Ernst A, Kaulich M. Circular synthesized CRISPR/Cas gRNAs for functional interrogations in the coding and noncoding genome. Elife. 2019 8: e42549. doi: 10.7554/eLife.42549. https://elifesciences.org/articles/42549
A picture may be downloaded here: http://www.uni-frankfurt.de/76899967
Caption: The team of Manuel Kaulich (2nd from right) in the laboratory. Credit: Uwe Dettmar
Further information: Dr. Kerstin Koch, Institut für Biochemie II, Universitätsklinikum, Tel.: +49 69 6301 84250, email@example.com
An experiment at GSI simulates how heavy elements capture protons
FRANKFURT. Heavy elements are produced during stellar explosion or on the surfaces of neutron stars through the capture of hydrogen nuclei (protons). This occurs at extremely high temperatures, but at relatively low energies. An international research team headed by Goethe University has now succeeded in investigating the capture of protons at the storage ring of the GSI Helmholtzzentrum für Schwerionenforschung.
As the scientists report in the current issue of Physical Review Letters, their goal was to determine more precisely the probability for a proton capture in astrophysical scenarios. As Dr. Jan Glorius from the GSI atomic physics research department explains, they were faced with two challenges in this endeavour: “The reactions are most probable under astrophysical circumstances in an energy range called the Gamow window. In this range, nuclei tend to be somewhat slow, making them difficult to obtain in the required intensity. In addition, the cross section – the probability of proton capture – decreases rapidly with energy. Until now, it has been almost impossible to create the right conditions in a laboratory for these kinds of reactions."
René Reifarth, Professor for experimental astrophysics at Goethe University suggested a solution as early as ten years ago: The low energies within the Gamow window range can be reached more precisely when the heavy reaction partner circulates in an accelerator in which it interact with an stationary proton gas. He achieved first successes in September 2015 with a group of Heimholtz early career researchers. Since then, his team has gained excellent support from Professor Yuri Litvinov, who leads the EU-funded research project ASTRUm at GSI.
In the experiment, the international team first produced xenon ions. They were decelerated in the experimental storage ring ESR and caused to interact with protons. This resulted in reactions in which the xenon nuclei captured a proton and were transformed into heavier caesium – a process like that which occurs in astrophysical scenarios.
“The experiment makes a decisive contribution to advancing our understanding of nucleosynthesis in the cosmos," says René Reifarth. “Thanks to the high-performance accelerator facility at GSI, we were able to improve the experimental technique for decelerating the heavy reaction partner. We now have more exact knowledge of the area in which the reaction rates occur, which until now had only been theoretically predicted. This allows us to more precisely model the production of elements in the universe."
The experiment took place as part of the research collaboration SPARC (Stored Particles Atomic Physics Research Collaboration), which is part of the FAIR research programme. Equipment funded by the Verbundforschung (collaborative research) of the Federal Ministry for Education and Research was used in this experiment.
A picture can be downloaded here: http://www.uni-frankfurt.de/76756294
Caption: For the first time, it was possible to investigate the fusion of hydrogen and xenon using an ion storage ring at the same temperatures as during stellar explosions. Credit: Mario Weigand, Goethe-Universität
Publication: J. Glorius et al: Approaching the Gamow window with stored ions: Direct measurement of 124Xe(p,γ) in the ESR storage ring, in PRL, DOI:10.1103/PhysRevLett.122.092701
Further information: Professor René Reifarth, Institute for Applied Physics at Goethe University, Riedberg Campus, Tel.: +49 69 798-47442, Reifarth@physik.uni-frankfurt.de.