Press releases

Acute-on-chronic liver failure (ACLF) is a common cause of death in patients with cirrhosis. In ACLF the progressive loss of function of the scarred liver can no longer be compensated (acute decompensation). As a result, other organs such as the kidney or brain fail. The triggers for acute decompensation of liver cirrhosis and an ACLF are most frequently bacterial infections, liver inflammation caused by alcohol, or a combination of both factors. This was revealed by the evaluation of the PREDICT study, which was conducted by an international team of researchers led by Professor Jonel Trebicka from the University Hospital Frankfurt.

FRANKFURT. Chronic liver disease and even cirrhosis can go unnoticed for a long time because many patients have no symptoms: the liver suffers silently. When the body is no longer able to compensate for the liver's declining performance, the condition deteriorates dramatically in a very short time: tissue fluid collects in the abdomen (ascites), internal bleeding occurs in the oesophagus and elsewhere, and the brain is at risk of being poisoned by metabolic products. This acute decompensation of liver cirrhosis can develop into acute-on-chronic liver failure with inflammatory reactions throughout the body and failure of several organs. 

In the PREDICT study, led by Professor Jonel Trebicka, scientists from 15 European countries observed 1273 patients who were hospitalized with acute decompensation of their liver cirrhosis. The current evaluation of the study focused on the question of what can trigger acute decompensation of liver cirrhosis. The result: in the vast majority of cases (>90%), a bacterial infection, liver inflammation caused by alcohol consumption, or both together could be identified as the trigger.

Bleeding in the digestive tract and brain dysfunction induced by painkillers or sedatives (drug-induced toxic encephalopathy) were identified as further trigger, although at a lower rate.

Lead investigator Professor Jonel Trebicka, gastroenterologist and hepatologist at the Medical Clinic I of the University Hospital Frankfurt, explains: "The acute decompensation of liver cirrhosis demands rapid and targeted action. In the PREDICT study, we therefore want to learn a lot about the triggering factors of this life-threatening disease in order to be able to derive recommendations for diagnostics and therapy. Knowing what the most likely triggers of acute decompensation are will help to further develop diagnostic and treatment strategies for patients with this life-threatening disease."

The pan-European PREDICT study has monitored the clinical course of acute decompensations of liver cirrhosis to find early signs of the development of acute-on-chronic liver failure (ACLF). PREDICT is funded by the European Foundation for the Study of Chronic Liver Failure. A total of 136 scientists from 47 centres and institutions in 15 European countries are participating in PREDICT.

Publication: Jonel Trebicka, Javier Fernandez, et al. for the PREDICT STUDY group of the EASL-CLIF CONSORTIUM: PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. Journal of Hepatology (2020), https://doi.org/10.1016/j.jhep.2020.11.019

Further information:
University Hospital Frankfurt, Goethe University Frankfurt
Medical Clinic I
Professor Jonel Trebicka
Section Translational Hepatology,
Medical Clinic I (Director: Professor Stefan Zeuzem)
Goethe University/University Hospital Frankfurt
Tel. +49 69 6301 80789 (Jennifer Biondo, secretarial office)
Jonel.Trebicka@kgu.de

The European Foundation for the Study of Chronic Liver Failure (EF Clif) is a private, non-profit Foundation whose mission is to promote study and research on Acute-on-Chronic Liver Failure and thus, contribute to improving both the quality of life and survival of patients with liver cirrhosis.
The EF Clif was created in 2015 to support the research work carried out by the EASL Clif Consortium, a research network of more than 100 European University Hospitals and 200 clinical investigators. In 2013, the Consortium described a new syndrome: Acute-on-Chronic Liver Failure (ACLF), which is the most common cause of death in cirrhosis.
Currently, the research activity of the EF Clif is fostered through two chairs: the EASL Clif Chair, to promote observational, pathophysiological and therapeutic studies through the EASL-Clif Consortium's hospital network; and the Grifols Chair, which promotes the development of translational research projects with the creation of a network of centres across Europe: The European Network for Translational Research in Chronic Liver Failure (ENTR-CLIF).
To know more about the EF Clif: http://www.efclif.com Twitter: @ef_clif

The economies of China and Singapore are among the most dynamic migration regions in the world. But Japan and Korea also rely on the immigration of skilled workers. The competition for qualified professionals sets several million people on the move in these regions every year. The role that skills and education play in mobility is now being investigated by scholars on East Asia from the universities of Frankfurt and Duisburg-Essen, the Free University of Berlin, and the Max Planck Institute for the Study of Multiethnic and Multireligious Societies in Göttingen. The junior research group coordinated by Goethe University will receive a total of more than 2 million euros from the Federal Ministry of Education and Research (BMBF) for the next four years as part of the "Small Subjects " funding initiative.

FRANKFURT. Aging societies in industrialised nations need skilled workers - specialists in the IT sector, in innovative start-ups, or from top universities. This applies to Germany as well as to the East Asian countries of South Korea, Singapore, China, and especially Japan. Because of their quality of life and lucrative renumeration, these countries are attractive for qualified migrants. But the recipe for success in the competition for the best brains is far from clear: What attracts well-trained specialists to Japan, South Korea, China, or Singapore? What facilitates, and what hinders the integration of skilled foreign workers? What social networks do skilled migrant workers develop? What role does their own initiative for further qualification, their ethnicity and nationality, their gender and multilingualism play? And what causes skilled workers to return to their home countries after years?

"If a country's immigration policy is to be sustainable," explains project leader Dr Ruth Achenbach from Goethe University, "then we need to know exactly what the perceptions of migrants are." The aim of the research project, which will receive funding by the BMBF of more than 2 million euros, is to examine the role of skills of migrant professionals. The researchers hope their findings will contribute to sustainable immigration policies in industrial nations.

In addition to Ruth Achenbach and Dr Joohyun Justine Park from the Interdisciplinary Centre for East Asian Studies (Goethe University), the academic team includes Dr Helena Hof (MPI Göttingen) as well as Dr Megha Wadhwa (Free University Berlin) and Dr Aimi Muranaka (University Duisburg-Essen). In addition, the researchers work with numerous external regional cooperation partners.

The research project will collect qualitative data in different East Asian countries over a period of three years. It will investigate the situation of East Asian start-ups in Japan and Singapore as well as East Asian professionals in South Korea; Chinese professionals in Japan, professionals who have returned to China, and Vietnamese IT workers and Indian professionals in Japan will also be interviewed. The Frankfurt sub-project also accompanies Chinese graduates of the 20 best Japanese universities from the beginning of their job-hunting to their first years on the labour market. 

In the final  year of funding, quantitative research will be conducted in the East Asin countries to test a theory developed from the qualitative research and previous migration research. In doing so, the researchers also aim to improve the dominant Western concepts of international migration research. Influenced by experiences of migration to America and Europe, these concepts assume that the economic situation in the country of origin and the country of immigration differ considerably. This is not necessarily the case anymore with East Asian labour migration and the project will differentiate between socioeconomic backgrounds of migrants.

The results of the empirical research as well as the development of theory will not only be published scientifically, but they will also be disseminated to the broader public. The project team’s dissemination activities include workshops for high school teachers in the subjects of politics and economics, and the release of a documentary film.

The researchers hope that their project will strengthen the "small subjects" by linking the researchers' knowledge of these regions with current research questions from sociology, political science and economics, thus increasing the visibility of the small subjects.

Further information:

Dr Ruth Achenbach
Interdisciplinary Centre for East Asian Studies

Goethe University Frankfurt

Telefon 069/798-23284
E-Mail: izo@uni-frankfurt.de

A short ten months after Goethe University and Frankfurt University Hospital first called for donations, the Goethe Coronavirus Fund has passed the targeted 5 million euro mark. The idea of the Goethe Coronavirus Fund came about in the first days of the pandemic: researchers require immediate and unbureaucratic support in order to make their contribution to overcoming the coronavirus crisis. More than 2000 private individuals, foundations and companies have meanwhile supported the goal of joining forces and providing competent help.

FRANKFURT. “Making a donation to research helped me overcome a feeling of helplessness during the first days of the coronavirus crisis,” says Raina Jockers, one of the more than 2000 donors for the Goethe Coronavirus Fund, explaining her motivation. The feelings of the Goethe University graduate are undoubtedly shared by many. The majority of donors contributed between 10 and 100 euros to the fund. The smallest donation came from the donation of bonus points from the “payback” programme and amounted to 2 cents; the largest was almost one million euros. Eight donors gave sums of more than 100,000 euros.

Using the non-profit online fundraising platform betterplace.org for the first time, the university’s call for donations reached even beyond Frankfurt citizens and foundations and companies from the Rhine-Main area, with donations coming in from Hamburg, Munich and even the USA. The fundraising platform also reported regularly on the work of the scientists, which may have motivated some donors to stick with it: one anonymous donor contributed 20 euros to the fund every month.

“In the pandemic, we wanted to help with what we do best: with our research,” says Professor Manfred Schubert-Zsilavecz, Goethe University Vice President. “So we simply jumped in at the deep end with our fundraising campaign and set ourselves an ambitious target: 5 million euros in donations. The fact that we have reached the 5 million euro mark in less than a year after our first call for donations makes us deeply grateful. Many private donors, as well as foundations and companies have been extremely generous. They funded research that helps us all,  keeping others in mind during this pandemic. This should really encourage us for the long road ahead.”

The Goethe Coronavirus Fund provided researchers at Goethe University and Frankfurt University Hospital with start-up support. Many of them have in the meantime raised additional funds for research having to do with SARS-CoV-2. The virologist Professor Sandra Ciesek and the infectologist Professor Maria Vehreschild, for example, are today part of the EU-funded CARE Consortium. Sandra Ciesek’s successes in drug research have made her one of the most prominent coronavirus researchers in Germany. Maria Vehreschild was one of the first to systematically collect clinical data and samples from COVID-19 patients and supplied her samples to vaccine and drug researchers throughout Germany; in the meantime, her database has been merged into a Germany-wide biobank.

But researchers from the social sciences and humanities have also profited from the Goethe Coronavirus Fund. More than 40 projects are now being funded – including the coronavirus crisis hotline, and studies by psychologist Professor Ulrich Stagnier on the psychological consequences of the pandemic.

The latest project supported by the Coronavirus Fund is dedicated to the work situation of healthcare workers and doctors in COVID-19 care in Hessian hospitals who are under particular strain. The cooperation project of the University Hospital Frankfurt and the Protestant University of Applied Sciences in Darmstadt first examines the effects on the employees. The results will be used to make recommendations for managers and healthcare workers, as well as concrete options for workplace health promotion. The evaluation of the first sub-study of the project is currently underway.

Further donations possible at: https://www.goethe-corona-fonds.betterplace.org and
through the donation account: Landesbank Hessen-Thüringen
IBAN: DE95 5005 0000 0001 0064 10
Reason for payment: Goethe-Corona-Fonds 

Scientists at Goethe University Frankfurt, together with colleagues from Darmstadt, Heidelberg, Oxford and Dundee (UK), have investigated how the fit of potent inhibitors to their binding sites can be optimised so that they engage longer with their target proteins. Long target residency has been associated with more efficient pharmacological responses for instance in cancer therapy. The result: High resolution structures revealed that when the interaction between the inhibitors and the target proteins lasts particularly long, the target proteins "nestle" against the inhibitors. In future, the researchers want to use computer simulations to predict the residence time of inhibitors during drug development.

FRANKFURT. Many anti-cancer drugs block signals in cancer cells that help degenerated cells to multiply uncontrollably and detach from tissue. For example, blocking the signalling protein FAK, a so-called kinase, causes breast cancer cells to become less mobile and thus less likely to metastasise. The problem is that when FAK is blocked by an inhibitor, the closely related signalling protein PYK2 becomes much more active and thus takes over some of FAK's tasks. The ideal would therefore be an inhibitor that inhibits both FAK and PYK2 in the same way for as long as possible.

An international team led by the pharmaceutical chemist Prof. Stefan Knapp from Goethe University has investigated a series of specially synthesised FAK inhibitors. All inhibitors bound to the FAK protein at about the same rate. However, they differed in the duration of binding: The most effective inhibitor remained bound to the FAK signalling protein the longest.

Using structural and molecular biological analyses as well as computer simulations, the research team discovered that binding of inhibitors that remain in the FAK binding pocket for a long time induce a structural change. Thus, through binding of these inhibitors, FAK changes its shape and forms a specific, water-repellent structure at contact sites with the inhibitor, comparable to an intimate embrace.

The closely related protein PYK2, on the other hand, remained comparatively rigid, and although the most effective FAK inhibitor also blocked PYK2, its effect was significantly weaker due to quickly dissociating inhibitors from the binding site. Interestingly, computer simulations were able to predict the kinetics of binding very well, providing a method for accurate simulation of drug dissociation rates for future optimisation of drug candidates.   

Prof. Stefan Knapp explains: "Because we now have a better understanding of the molecular mechanisms of the interaction of potent inhibitors of these two kinases, we hope to be able to use computer simulations to better predict drug residence times of inhibitors and drugs candidates in the future. So far, little attention has been paid to the kinetic properties of drug binding. However, this property has now emerged as an important parameter for the development of more effective drugs that are designed to inhibit their target proteins - as in the case of FAK and PYK2 - not only potently but also for a long time."

Publication: Benedict-Tilman Berger, Marta Amaral, Daria B. Kokh, Ariane Nunes-Alves, Djordje Musil, Timo Heinrich, Martin Schröder, Rebecca Neil, Jing Wang, Iva Navratilova, Joerg Bomke, Jonathan M. Elkins, Susanne Müller, Matthias Frech, Rebecca C. Wade, Stefan Knapp: Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2. Cell Chemical Biology https://doi.org/10.1016/j.chembiol.2021.01.003

This work was carried out within the framework of the public-private partnership K4DD (Kinetics for Drug Discovery) of the Innovative Medicinces Initiatives (IMI). https://www.k4dd.eu/home/

Images for download:
Picture with and without text: http://www.uni-frankfurt.de/96999809

Caption:
Upper part: Long residence time. An inhibitor (left: stick model) binds to the signal molecule FAK (right: part oft the FAK protein depicted as calotte model with spheres). The structural change of FAK causes hydrophobic contacts (yellow, so-called DFG motif) and a long-lasting engagement.
Lower part: Short residence time. PYK2 signal protein does not change its structure upon inhibitor binding, thus resulting in a fast inhibitor dissociation. Graphics: Knapp Laboratory, Goethe University Frankfurt

Further information:
Professor Stefan Knapp
Institute for Pharmaceutical Chemistry
Goethe University Frankfurt
Germany
knapp@pharmchem.uni-frankfurt.de

Bacteria act in groups to accomplish feats that are impossible to achieve if a single bacterium acts alone. For example, pathogenic bacteria act collectively to synthesize toxins to attack the host and to encase themselves in a shield that protects them from the host immune system and allows them to resist antibiotic treatment. To do this, bacteria communicate with each other with chemical “words", count their numbers, and act in synchrony when they have sufficient cell numbers for success. The award winners have discovered the dictionary and syntax underlying bacterial communication, opening up new and unprecedented opportunities to fight bacterial infections.

FRANKFURT am MAIN. Two American scientists, Bonnie L. Bassler and Michael R. Silverman, receive the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize, which is endowed with 120,000 €. Bassler is Professor at Princeton University and a Howard Hughes Medical Institute Investigator, Michael R. Silverman is Emeritus Professor of the Agouron Institute in La Jolla. The two researchers are honoured for their ground-breaking discoveries concerning bacterial "quorum sensing", which refers to sophisticated systems of cell-to-cell communication that bacteria use to coordinate group behaviours. The award ceremony in St. Paul's Church, which is traditionally held on March 14, Paul Ehrlich's birthday, has been postponed due to the Coronavirus pandemic. Instead, Bassler and Silverman will receive the award at the ceremony in 2022.

"Silverman and Bassler have shown that, as for multicellular organisms, collective behaviour is the rule among bacteria, rather than the exception," wrote the Scientific Council in substantiating its decision. "Bacteria talk to each other, they eavesdrop on other bacteria, and they may even join forces. But: This ubiquitous chitchat, whose molecular underpinnings were discovered by Bassler and Silverman, also represents a previously unappreciated Achilles' heel in combating harmful microbes. Instead of killing bacteria with antibiotics, substances may be developed that interfere with bacterial communication effectively reducing their collective fitness. The prize-winners' research thus has considerable relevance for medicine".

Bacteria are extremely communicative. They send and receive chemical messages to find out whether they are alone or if additional members of their or other species are present in the vicinal community. To take a census of cell numbers, bacteria produce and release chemical signal molecules that accumulate in step with increasing cell numbers. When a threshold level of the chemical signal is achieved, the bacteria detect its presence. In response to it, in unison, bacteria undertake behaviours that are only productive when carried out in synchrony by the group, but not when enacted by a single bacterium acting in isolation. This chemical communication process is called quorum sensing and it controls hundreds of collective activities across the bacterial kingdom.

In the 1980s, Silverman discovered the first quorum-sensing circuit in the bioluminescent marine bacterium Vibrio fischeri. He identified the genes and proteins enabling production and detection of the extracellular signal molecule. He defined how the components functioned to promote collective behaviour. In the case of Vibrio fischeri, group-wide behaviour is the production of blue-green bioluminescence. Today, we know that quorum sensing is the norm in the bacterial world. Indeed, there are thousands of bacterial species that possess genes nearly identical to those discovered by Silverman. In all of these cases, these components allow bacteria to engage in group behaviours.

In the early 1990s, Bonnie Bassler proved that bacteria were “multilingual" and that they conversed with multiple chemical signal molecules. One communication molecule that Bassler discovered and named autoinducer- 2 enables bacteria to communicate across species boundaries. She went on to demonstrate that bacteria use quorum-sensing-mediated communication to differentiate self from other, showing that a sophisticated trait thought to be the purview of higher organisms, in fact, evolved in bacteria billions of years ago. In recent years, Bassler has shown that quorum sensing transcends kingdom boundaries as viruses and host cells, including human cells, engage in this ubiquitous chit-chat. She and other researchers also demonstrated that pathogenic bacteria rely on quorum sensing to be virulent. Bassler developed anti-quorum-sensing strategies that, in animal models, halt infection from bacterial pathogens of global significance.

“The full significance of the discoveries of the two laureates for microbiology and medicine has only recently been recognized," says Professor Thomas Boehm, Director at the Max Planck Institute for Immunobiology and Epigenetic and Chairman of the Scientific Council. "Decades of meticulous and painstaking work, showed that essentially all bacteria master the art of cell-to-cell communication," says Boehm. "What began with work on Vibrio fischeri and Vibro harveyi led to a fundamental change in perspective in bacteriology, and now opens up new and unprecedented opportunities in dealing with antibiotic resistance".

Short biography Professor Dr. Bonnie L. Bassler Ph.D. (58).

Bonnie Bassler is a microbiologist. She studied biochemistry at the University of California at Davis and received her Ph.D. from the Johns Hopkins University in Baltimore. She joined the laboratory of Michael Silverman at the Agouron Institute in La Jolla as a postdoctoral fellow in 1990. She has been at Princeton University since 1994. Bonnie Bassler is a member of the National Academy of Sciences, the National Academy of Medicine, and the Royal Society. She is a researcher at the Howard Hughes Medical Institute and Squibb Professor and Chair of the Department of Molecular Biology at Princeton University. President Obama appointed her to a six-year term on the United States National Science Board. She has received more than twenty prestigious national and international awards.

Short biography Professor Michael R. Silverman, Ph.D. (77).

Michael Silverman is a microbiologist. He studied chemistry and bacteriology at the University of Nebraska at Lincoln and received his Ph.D. in 1972 from the University of California at San Diego. During the period from 1972-1982, Silverman made seminal contributions to the understanding of bacterial motility and chemotaxis. From 1982 until his retirement, he worked at the Agouron Institute in La Jolla, of which he is a co-founder.

The Paul Ehrlich and Ludwig Darmstaedter Prize
The Paul Ehrlich and Ludwig Darmstaedter Prize is traditionally awarded on Paul Ehrlich's birthday, March 14, in the Paulskirche, Frankfurt. It honors scientists who have made significant contributions in Paul Ehrlich's field of research, in particular immunology, cancer research, microbiology, and chemotherapy. The Prize, which has been awarded since 1952, is financed by the German Federal Ministry of Health, the State of Hesse, the German association of research-based pharmaceutical company vfa e.V. and specially earmarked donations from the following companies, foundations and organizations: Else Kröner-Fresenius-Stiftung, Sanofi-Aventis Deutschland GmbH, C.H. Boehringer Pharma GmbH & Co. KG, Biotest AG, Hans und Wolfgang Schleussner-Stiftung, Fresenius SE & Co. KGaA, F. Hoffmann-LaRoche Ltd., Grünenthal GmbH, Janssen-Cilag GmbH, Merck KGaA, Bayer AG, Holtzbrinck Publishing Group, AbbVie Deutschland GmbH & Co. KG, die Baden-Württembergische Bank, B. Metzler seel. Sohn & Co. and Goethe-Universität. The prizewinners are selected by the Scientific Council of the Paul Ehrlich Foundation.

The Paul Ehrlich Foundation
The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president of the German Research Foundation, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Thomas Boehm, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.

Further information:
You can obtain selected publications, the list of publications and a photograph of the laureate from Dr. Hildegard Kaulen, phone: +49 (0)6122/52718, email: h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de

Background on the award of the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize to Professor Bonnie L. Bassler, Ph.D. and Professor Michael R. Silverman, Ph.D.