Press releases – 2020

 

Sep 29 2020
10:40

Substance with new mechanism of action found

A cancer shredder

FRANKFURT. Researchers at Goethe University Frankfurt and the university of Würzburg have developed a new compound for treating cancer. It destroys a protein that triggers its development.

The villain in this drama has a pretty name: Aurora – Latin for dawn. In the world of biochemistry, however, Aurora (more precisely: Aurora-A kinase) stands for a protein that causes extensive damage. There, it has been known for a long time that Aurora often causes cancer. It triggers the development of leukemias and many pediatric cancers, such as neuroblastomas.

Researchers at the universities of Frankfurt and Würzburg have now developed a drug that can disarm Aurora. Stefan Knapp, Professor of Pharmaceutical Chemistry at Goethe University Frankfurt, and Dr. Elmar Wolf, biochemist and research group leader at the Biocenter of Julius-Maximilians-Universität Würzburg (JMU), have played a leading role in this development. The results of their work have now been published in the latest issue of Nature Chemical Biology.

Making tumor-promoting proteins disappear

Cancers are usually triggered by tumorigenic proteins. Because cancer cells produce more of these proteins than normal cells, the dynamics are additionally increased. A common therapeutic approach is therefore to inhibit the function of these proteins with drugs. Although the proteins are then still there, they no longer function as well. This makes it possible to combat the tumor cells.
 
However, the development of these inhibitors is difficult and has so far not been successful for all tumor-promoting proteins. To date, none of the candidates that inhibit Aurora has shown the desired results in clinical practice. The dream of many scientists is therefore to develop a drug that not only inhibits the tumor-promoting proteins but makes them disappear completely. A promising approach along this path could be a new class of substances with the scientific name “PROTAC".

In vitro cancer cells die

“We have developed such a PROTAC for Aurora," says Elmar Wolf. This PROTAC completely degrades the Aurora protein in cancer cells. Such cells cultivated in the laboratory died as a result. Wolf describes the mode of action of this substance as follows: “The tumor needs certain tumor-promoting proteins, which we can imagine as the pages of a book. Our PROTAC substance tears out the 'Aurora' pages and destroys them with the help of the machinery that every cell has to degrade old and broken proteins." PROTAC thus “shreds" the Aurora protein, as it were, until nothing of it remains.

Professor Stefan Knapp from the Institute of Pharmaceutical Chemistry at Goethe University explains: “Aurora-A kinase is present in much higher concentrations in many cancer tissues than in healthy tissue and it also plays a key role in prostate cancer. Blocking the activity of Aurora-A kinase alone seems not a promising approach as none of the many clinically tested drug candidates has achieved clinical approval. With our PROTAC variant, we inhibit Aurora-A kinase via another, possibly more effective mechanism, which may open up new treatment options. That's why in the next step we'll test effectiveness and tolerance in animal models."


Publication: PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase. Bikash Adhikari, Jelena Bozilovic, Mathias Diebold, Jessica Denise Schwarz, Julia Hofstetter, Martin Schröder, Marek Wanior, Ashwin Narain, Markus Vogt, Nevenka Dudvarski Stankovic, Apoorva Baluapuri, Lars Schönemann, Lorenz Eing, Pranjali Bhandare, Bernhard Kuster, Andreas Schlosser, Stephanie Heinzlmeir, Christoph Sotriffer, Stefan Knapp and Elmar Wolf. Nature Chemical Biology, 28.09.2020. https://www.nature.com/articles/s41589-020-00652-y

PROTACS: The cluster project PROXIDRUGS at Goethe University Frankfurt focuses on PROTACS (Proteolysis Targeting Chimeric Molecules): https://aktuelles.uni-frankfurt.de/englisch/proxidrugs-project-led-by-goethe-university-included-in-clusters4future-programme/

Further Information:
Prof. Dr. Stefan Knapp
Institut of Pharmaceutical Chemistry
Goethe University Frankfurt
Phone: +49 69 798 29871
knapp@pharmchem.uni-frankfurt.de

 

Sep 22 2020
15:33

​Grant allows conservation of valuable collection owned by the Department for Children’s and Young Adult Literature Research at Goethe University.

Walter Benjamin’s collection of children’s books to be restored

FRANKFURT. Walter Benjamin's collection of children's books is to be saved for posterity. The national government, the Federal State of Hesse and the Department for Children's and Young Adult Literature Research have joined forces to finance the first restoration work on this valuable historical archive.

The collection previously owned by Walter Benjamin comprises just 204 books. Yet it is particularly valuable in several respects: For research, it delivers important insights into this great intellectual mind, who was a close friend of Theodor W. Adorno and belonged to the circle of the Frankfurt School. Some of the books stem from Benjamin's own childhood, and in his writings and radio broadcasts he also dealt with children's literature based on his collection. Moreover, the collection is composed entirely of beautiful and rare copies: Benjamin, who was born in Berlin, primarily built up his collection according to aesthetic criteria; he was especially interested in illustrated and artistically ornate children's books.

Having been purchased from Benjamin's heirs, the collection came to the Department for Children's and Young Adult Literature Research in the 1980s. It was the explicit wish of Stefan Benjamin, Walter Benjamin's son, that the collection return to Germany. It was displayed at an exhibition at the University Library and an elaborate catalogue was produced (available for download from the department's website: www.uni-frankfurt.de/65668457/Die_Kinderbuchsammlung_Walter_Benjamin_Katalog.pdf).

Since then, the books have been kept in a steel cabinet in the department's library. To be able to continue making them accessible for research, restoration work is urgently required: The books are used a great deal and partially damaged as a result, the ravages of time have done the rest. They will now first be “stabilised". Part of the collection has already been sent to the Centre for Book Conservation in Leipzig, where first of all the paper will be deacidified, the cover and edges stabilised, and customised boxes with hinged lids made for each individual book.

“With modest means, Benjamin assembled the books from his own childhood into a collection," explains Dr Felix Giesa, custodian at the Department for Children's and Young Adult Literature Research. He primarily collected books according to aesthetic criteria, he adds, mostly illustrated works from the 19th century. Apart from various editions of Grimms' Children's and Household Tales, fairytales by Wilhelm Hauff and Charles Perrault are also part of the collection. In addition, what are known as transformation picture books, such as a rare book by Christian Gottfried Heinrich Geissler dated 1815, make up an important part of the valuable collection.

With funds from the government's Coordination Office for the Preservation of Written Cultural Heritage, which will assume 50 percent of the costs, from the Federal State of Hesse, which will bear 40 percent via the Hessian Ministry of Higher Education, Research, Science and the Arts, and from the budget of Professor Ute Dettmar, the collection will first be stabilised and catalogued, after which an exhibition and a symposium are planned. A total of around € 30,000 is available for these measures. Later, the collection will also be digitised so that it is available for Benjamin research in Germany and abroad – without its use leaving further traces in the originals.


Images can be downloaded under the following link: http://www.uni-frankfurt.de/92258379

Caption: Much-used and correspondingly worse for wear: Walter Benjamin's collection of children's books is to be saved for posterity. Funds for this are now available. (Photo: Uwe Dettmar)

 

Sep 21 2020
11:38

Physicists at Goethe University lead one of the technical refurbishments of “ALICE” for researching quark-gluon plasma

Physics: Collision movie with upgraded particle detector at CERN

The ALICE experiment at the particle accelerator CERN in Geneva has the aim of providing new insights into an extremely hot and dense state of matter, the quark-gluon plasma. The entire matter of the universe was in this state just a few millionths of a second after the big bang, and the ALICE experiment will help researchers discover how the universe developed out of this primordial soup. An international team of scientists led by the physicist Harald Appelshäuser from Goethe University Frankfurt have therefore upgraded the centrepiece of the ALICE detector to current state of the art technology.

FRANKFURT. For the moment, the accelerators at CERN are at rest during the “second long shutdown". During this time, the accelerators undergo upgrades and refurbishments so that more particles can be accelerated and the number of collisions will increase in the future. The detectors are also undergoing upgrades. But while the large all-purpose detectors ATLAS and CMS are not scheduled for larger upgrades until the next, and third long shutdown in 2025, the specialised detector ALICE will enter the upcoming measurement campaign already upgraded.

ALICE is a unique project among the research adventures surrounding CERN's Large Hadron Collider (LHC). While the other three detectors decipher what occurs in collisions of protons, the researchers in the ALICE experiment are concerned with lead ions – particles that are many times heavier. Each year, the LHC is operated with lead ions for one month so that the ALICE detector can collect data. The researchers want to learn more about a particular state of matter: quark-gluon-plasma. It is created inside the ALICE experiment when lead nuclei collide with each other at high energy and are dissolved into their elementary components for a short moment. In this hot and dense soup of matter, quarks and gluons, otherwise firmly attached in the protons and neutrons, can move around virtually freely. What happens during the collisions may provide insight into how our universe as we know it today was formed out of a giant primordial out of quark-gluon plasma.

Recording a movie instead of taking individual pictures

After the shutdown, the upgraded ALICE detector will show what it can now do: previously, the LHC accelerator delivered 10,000 collisions per second. At 18,000 particles per collision this amounts to 180 million particles per second, only a portion of which was able to be recorded by the ALICE detector. After the shutdown, the technological hurdles which have until now limited the number of recorded collisions will have been eliminated. The LHC should then deliver 50,000 collisions of lead ions per second, resulting in 900 million particles per second. “We want to record all collisions in entirety and, in fact, continuously, in other words, to record a movie instead of individual pictures," explains Harald Appelshäuser, Professor at the Institute for Nuclear Physics at Goethe University Frankfurt and project leader of the subdetector that will make the biggest difference after the upgrade.

Detector under construction

To achieve this, one of the central detectors of the 26-metre long and 16-metre high ALICE detector complex, the Time Projection Chamber (TPC), was removed and carefully brought from the underground detector cavern into a clean room on the surface. Different parts that were developed all over the world during the past several years were gradually and carefully installed. Now the technologically upgraded TPC has been returned to its home at the heart of ALICE.

The highlights are the new readout chambers which no longer consist of many fine wires, but basically of about five billion tiny holes. In these holes, the signals of the charged particles will be amplified so that the scientists can precisely calculate the track of each particle. These chambers are called “GEMs" – Gas Electron Multipliers – and are a CERN invention which has already found its way into medical procedures. 500,000 channels ensure that nothing escapes the ALICE experiment. Each second during the collisions later results in 3.4 terabytes of data.

New procedures must also be developed which can process this flood of data. With the participation of high-performance computing expert Professor Volker Lindenstruth and his colleagues, scientists from Goethe University will be playing a leading role here as well.  “We now have the finest of the fine and look forward to the first collisions," says Appelshäuser.

The new GEM readout chambers were custom fit for the ALICE experiment through testing and development in Germany – at Goethe University Frankfurt as well as at the Bonn and Heidelberg Universities, the Technical University Munich, and the GSI Helmholtzzentrum für Schwerionenforschung, and later assembled in different countries which in addition to Germany included Hungary, Finland, Romania and the USA. “The logistics were pretty complicated," explains project leader Appelshäuser. “The TPC was brought to the clean room in 2019 that was where we removed the older chambers and installed and tested the new ones. Luckily, we had just finished before the pandemic started."

During the shutdown ALICE will also receive a new inner tracking chamber, positioned closer to the collision point and further increasing precision compared to its predecessor. And the detectors have to be precise, for only through exact determination of particle paths and particle energies can conclusions be reached about the first split seconds of the universe.

Images may be downloaded here: http://www.uni-frankfurt.de/92047073

Caption: Working on the ALICE detector under corona conditions: from the left: Robert Münzer (Goethe University Frankfurt, GU), Chilo Garabatos (GSI Helmholtzzentrum für Schwerionenforschung), Lars Bratrud (GU), Yiota Chatzidaki (Heidelberg University), Christian Lippmann (GSI).
Credit: Robert Münzer

Additional images for download at CERN:
https://cds.cern.ch/record/2727174#

Further information:
Prof. Dr. Harald Appelshäuser
Institute for Nuclear Physics
Goethe University
Phone: +49 69 798-47034 or 47023
appels@ikf.uni-frankfurt.de

 

Sep 3 2020
14:27

Archaeologists from Frankfurt and Munich prove origins in the first millennium B.C.

New dating of Nebra sky disk

FRANKFURT. Until now the Nebra sky disk was deemed to be from the Early Bronze Age and therefore the world's oldest depiction of the cosmos. Archaeologists from Goethe University Frankfurt and Ludwig-Maximilian University in Munich have now reanalysed diverse data on the reconstruction of the discovery site and surrounding circumstances of the find. Their findings are that the disk must be dated in the Iron Age, making it about 1,000 years younger than previously assumed. This makes all previous astronomical interpretations obsolete. 

The Nebra sky disk is one of Germany's most significant archaeological finds and was included in the UNESCO Memory of the World Register in 2013. It was discovered in an illegal excavation in 1999 together with Bronze Age swords, axes and bracelets according to the finders. This discovery context was important for the scientific dating, as the disk itself could neither be scientifically nor archeologically dated by comparison with other objects. Many years of investigations by several research groups therefore attempted to verify both the attribution to the supposed discovery site as well as the common origins of the objects independent of the vague information given by the looters.

Rupert Gebhard, Director of the Munich Archäologischen Staatssammlung, and Rüdiger Krause Professor for Prehistory and Early European History at Goethe University Frankfurt have now extensively analysed the discovery circumstances and research results on the Nebra sky disk. Their conclusion: The site that was considered the discovery site until today and which was investigated in subsequent excavations is with high probability not the discovery site of the looters. Furthermore, there is no convincing evidence that the Bronze Age swords, axes and bracelets form an ensemble of common origins. For this reason, it must be assumed that this is not a typical Bronze Age deposit and that the disk was not found together with the other objects in an original state at the excavation site.

According to the archaeologists, this means that the disk must be investigated and evaluated as an individual find. Culturally and stylistically, the sky disk cannot be fitted into the Early Bronze Age motif world of the beginning of the second millennium B.C. On the contrary, clearer references can be made to the motif world of the Iron Age of the first millennium B.C. According to Gebhard and Krause, on the basis of a divergent data situation and on the basis of this new assessment, all previous, sometimes far-reaching cultural-historical conclusions must be discussed anew and with an open mind, and the disk must be interpreted and evaluated in different contexts than before. The basis for this must be the submission of all previously unpublished data and facts.

More detailed information can be found on the website of the Deutsche Gesellschaft für Ur- und Frühgeschichte (German Society for Prehistory and Early History) https://dguf.de/himmelsscheibe.html

Publication: Rupert Gebhard & Rüdiger Krause, Critical comments on the find complex of the so-called Nebra Sky Disk. In: Archäologische Informationen. Early View: citable online version with preliminary page numbering. After the printed volume is published, the final page numbers can be found in open access here: http://journals.ub.uni-heidelberg.de/arch-inf. The printed volume can be obtained here: http://www.archaeologische-informationen.de

Image download: http://www.uni-frankfurt.de/91701141

Captions:
1. The condition of the Nebra sky disk before being transferred to the Landesmuseum Halle an der Saale. Credit: Hildegard Burri-Bayer
2. Bronze Age swords, axes and bracelets, supposedly found together with the Nebra sky disk. Condition before being transferred to the Landesmuseum Halle an der Saale. Credit: Hildegard Burri-Bayer

Further information:
Prof. Dr. Rüdiger Krause
Prof. Dr. Rupert Gebhard
through
Press Office of Goethe University Frankfurt
Dr Markus Bernards
Tel. +49 (0)69 798 12498
bernards@em.uni-frankfurt.de

 

Aug 26 2020
15:30

International research group identifies three forms of disease progression for “acute decompensated liver cirrhosis” 

  When liver cirrhosis is deadly 

FRANKFURT. When the body can no longer compensate the gradual failure of the liver caused by liver cirrhosis, there is a high risk of acute decompensated liver cirrhosis. In some patients this develops quickly into an often deadly acute-on-chronic liver failure, in which other organs such as the kidneys or brain fail. A study by an international team of researchers headed by Professor Jonel Trebicka from the Frankfurt University Hospital and funded by the foundation EF Clif, has discovered which patients are particularly at risk. With their findings, the scientists have laid the foundation for the development of preventive therapy to prevent acute-on-chronic liver failure. 

The liver has many functions: it stores nutrients and vitamins, produces dextrose, coagulation factors and hormones, and breaks down toxins, drugs and alcohol. Chronic alcohol abuse, viruses or other diseases can damage the liver and lead to chronic liver disease. Without treatment, chronic liver disease leads to liver cirrhosis in the final stages, in which liver tissue turns into connective tissue, making the liver increasingly unable to carry out its functions. The result: the blood’s clotting ability is impaired, toxic metabolic products are fortified, the liver is not adequately supplied with blood and blood pressure rises in the portal veins that supply the liver.

The body tries to compensate for the reduced liver function. For example, new veins develop as alternative circulation from the oesophagus, stomach and intestines which expand into varicose veins. When the disease progresses to the point that this kind of compensation is no longer possible – physicians speak of acute decompensated liver cirrhosis – the situation becomes life-threatening: tissue fluid (ascites) collects in the abdominal cavity, leading to bacterial infections and internal bleeding, for example in the oesophagus. Difficulty concentrating, mood swings and sleepiness are signs of a poisoning of the brain (hepatic encephalopathy) that can result in a hepatic coma.

A European clinical study headed by Professor Jonel Trebicka, and carried out under the umbrella of the European Foundation for the Study of Chronic Liver Failure, has for the first time identified three clinical course variations in patients admitted to the hospital with acute decompensated cirrhosis.

1.    The first clinical course is characterised by high blood inflammation values, indicating inflammatory reactions throughout the body. Within three months after admission to the hospital, a number of body organs fail: the acute decompensation becomes “acute-on-chronic liver failure” (ACLF). The physicians therefore call this variation Pre-ACLF. More than half of patients die from it; only a third survive after a year.

2.    Patients with the second clinical course do not develop ACLF and have moderate inflammation values. They suffer, however, from significant hypertension in the portal vein. Approximately 20 percent die within the following three months, another 15 percent over the course of the following year. The physicians named this variation “instable decompensated liver cirrhosis”.

3.    The patients with the third clinical course exhibit neither high inflammation values nor frequent complications. They do not develop ACLF in the first three months. Within a year, however, one in ten dies. The physicians call this variation “stable decompensated liver cirrhosis.“

Lead investigator Professor Jonel Trebicka, gastroenterologist and hepatologist at Medical Clinic I of  University Hospital Frankfurt explains: “We are now working intensively on the development of new diagnostic options, especially for the group of pre-ACLF patients, in order to identify this group before admission to the hospital so that preventive measures can be implemented early on. The development of preventive therapies for the often deadly ACLF is one of our most important research goals in this context.”

Study co-author Professor Stefan Zeuzem, Dean of the Faculty of Medicine and Director of Medical Clinic I at Frankfurt University Hospital explains: “Liver diseases are one of the main focal points of Medical Clinic I and we offer numerous specialised outpatient departments for patients with acute and chronic liver diseases. So on the one hand we were able to observe patients for the study. On the other hand, the research findings on improving ACLF prevention and therapies will rapidly benefit all of our patients.”

The research findings are part of a European-wide study called PREDICT. The study observes the clinical course of acute decompensated liver cirrhosis in order to find early indications for the development of acute-on-chronic liver failures (ACLF). The study was funded by the European Foundation for the Study of Chronic Liver Failure. 136 scientists from 47 centres and institutions in 14 European countries are participating in PREDICT.

Publication: Jonel Trebicka, Javier Fernandez, Maria Papp, Paolo Caraceni, Wim Laleman, Carmine Gambino, et al.: The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. Journal of Hepatology, https://doi.org/10.1016/j.jhep.2020.06.013

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.