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Researchers in Frankfurt discover new mechanism of chemotherapy resistance in colon cancer
Researchers at Georg-Speyer-Haus and Goethe University Frankfurt have discovered a new mechanism that explains why only some of the cells in a colon tumour respond to chemotherapy. The research team led by Professor Florian Greten was able to establish that tumour cells dying off during chemotherapy communicate one last time with neighbouring tumour cells to give them instructions on how to resist the therapy. The dying cells re-programme the signalling cascades in the neighbouring tumour cells in such a way that these are no longer vulnerable to chemotherapy. By doing so, the dying cells literally ensure that the tumour survives.
FRANKFURT. Colorectal carcinoma is the second most common cause of cancer death in Germany. Although cancer research in recent years has been able to significantly improve early diagnosis and therapy, the resistance of advanced colorectal tumours to common chemotherapies still constitutes a major problem and contributes substantially to the high mortality rate of patients with such tumours.
When chemotherapeutic agents cause colon cancer cells to die, they release ATP (adenosine triphosphate) molecules, the cell's energy currency, as a messenger substance. Researchers led by Professor Florian Greten at Georg-Speyer-Haus have now corroborated this in experiments. This ATP binds to certain receptors (P2X4 purinoreceptors) on the surface of surrounding tumour cells. This activates an important survival signalling pathway in these neighbouring cells, which protects them from cell death and makes the tumour resistant to therapy.
The cells killed off by the chemotherapy “warn" their neighbouring cells, as it were, and at the same time provide them with a survival strategy. However, if the communication between the dying tumour cells and their neighbours is interrupted – as the scientists were able to show in preclinical models – this raises the efficiency of the chemotherapy many times over, and tumours that were initially resistant respond very well to it.
Dr. Mark Schmitt, first author of the study, explains: “Our research results demonstrate that – despite years of successful research – unknown mechanisms are still being discovered which show us how perfidiously tumour cells evade therapy. Our results now offer a new and promising starting point for substantially improving the response rate of advanced colorectal carcinomas to common chemotherapeutic agents by means of combination therapy."
Professor Florian Greten, director of Georg-Speyer-Haus and spokesperson for the LOEWE Centre Frankfurt Cancer Institute explains: “We were surprised to see that tumour cells have developed communication mechanisms to the point that even the dying ones play an active role in ensuring their neighbours' survival when under therapeutic 'attack'. We hope very much that by interrupting the communication between the cells we can achieve this tremendous increase in the effect of standard therapy in patients as well." The team now wants to work with colleagues at the Frankfurt Cancer Institute to test this new therapeutic concept in patients.
Publication: Mark Schmitt, Fatih Ceteci, Jalaj Gupta, Marina Pesic, Tim W. Böttger, Adele M. Nicolas, Kilian B. Kennel, Esther Engel, Matthias Schewe, Asude Kirisozu, Valentina Petrocelli, Yasamin Dabiri, Julia Varga, Mallika Ramakrishnan, Madina Karimova, Andrea Ablasser, Toshiro Sato, Melek C. Arkan, Frederic J. de Sauvage & Florian R. Greten: Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation. Nature (2022) https://doi.org/10.1038/s41586-022-05426-1
Picture download: https://www.uni-frankfurt.de/128472339
Captions: Prof. Dr. Florian Greten, Georg-Speyer Haus. Foto: Uwe Dettmar für Goethe-Universität-Frankfurt Dr. Mark Schmitt, Foto: Eliana Stanganello
Professor Florian R. Greten
Georg-Speyer-Haus / Goethe University Frankfurt
Institute for Tumour Biology and Experimental Therapy
Tel.: +49 (0)69 63395-232
Global study’s ranking includes the one percent of scientists cited most frequently
Six of the nearly 7,000 most cited scientists in the world conduct research at Goethe University Frankfurt. That is the result of the current citation ranking of the "Web of Science", published by Clarivate Analytics.
FRANKFURT. In most cases, it is fundamental scientific findings that result in a paper being cited frequently by other scientists. That is why citation frequency serves as an indicator of the published articles' scientific significance as well as the authors' visibility in the scientific community.
Once a year, information and technology company Clarivate Analytics evaluates its "Web of Science" citation database and publishes the "Highly Cited Researchers" ranking. The current ranking includes 6,938 scientists, in no particular order, who belonged to the one percent of authors whose scientific articles in the natural and engineering sciences, medicine, and the categories "Economics and Business" and "Social Sciences" were cited most frequently between 2011 and 2021, either within their own category or in different subjects ("cross-field").
Here are the "highly cited" Goethe researchers of 2022:
Professor Ivan Đikić
Director of Goethe University's Institute for Biochemistry II (Molecular Cell Biochemistry)
in the categories “Molecular Biology" and “Genetics"
Professor Stefanie Dimmeler
Director of Goethe University's Institute of Cardiovascular Regeneration / Institute for Molecular Medicine / German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung, DZHK) / Spokeswoman of the Cardio-Pulmonary Institute (CPI) excellence cluster jointly operated by Goethe University, Justus-Liebig-University Gießen and the Max-Planck-Institute for Heart and Lung Research
in the category “Cross Field"
Professor Petra Döll
Managing Director of Goethe University's Institute of Physical Geography
in the category “Cross Field"
Professor Stefan Knapp
Goethe University's Institute of Pharmaceutical Chemistry
in the category “Cross Field"
apl. Professor Sibylle Loibl
Goethe University Faculty of Medicine / German Breast Group Forschungs GmbH, Neu-Isenburg
in the category “Clinical Medicine"
Professor Stefan Zeuzem
Dean of Goethe University's Faculty of Medicine / Director of Medical Clinic I – Gastroenterology and Hepatology, Pneumology and Allergology, Endocrinology and Diabetology, as well as Nutritional Medicine
in the category “Clinical Medicine"
Images for download: https://www.uni-frankfurt.de/128363352
Professor Ivan Đikić, Goethe University Frankfurt, Photo: Uwe Dettmar for Goethe University
Professor Stefanie Dimmeler, Goethe University Frankfurt Photo: Uwe Dettmar for Goethe University
Professor Petra Döll, Goethe University Frankfurt, Photo: Jürgen Lecher for Goethe University
Professor Stefan Knapp, Goethe University Frankfurt, Photo: Uwe Dettmar for Goethe University
apl. Professor Sibylle Loibl, Goethe University Frankfurt, Photo: Joppen for GBG Forschungs GmbH
Professor Stefan Zeuzem, Goethe University Frankfurt, Photo: Uwe Dettmar for Goethe University
Physicists at Goethe University model more than one million equations of state
Through extensive model calculations, physicists at Goethe University Frankfurt have reached general conclusions about the internal structure of neutron stars, where matter reaches enormous densities: depending on their mass, the stars can have a core that is either very stiff or very soft. The findings were published simultaneously in two articles today (The Astrophysical Journal Letters, DOI 10.3847/2041-8213/ac9b2a, DOI 10.3847/2041-8213/ac8674).
FRANKFURT. So far, little is known about the interior of neutron stars, those extremely compact objects that can form after the death of a star: the mass of our sun or even more is compressed into a sphere with the diameter of a large city. Since their discovery more than 60 years ago, scientists have been trying to decipher their structure. The greatest challenge is to simulate the extreme conditions inside neutron stars, as they can hardly be recreated on Earth in the laboratory. There are therefore many models in which various properties – from density and temperature – are described with the help of so-called equations of state. These equations attempt to describe the structure of neutron stars from the stellar surface to the inner core.
Now physicists at Goethe University Frankfurt have succeeded in adding further crucial pieces to the puzzle. The working group led by Prof. Luciano Rezzolla at the Institute of Theoretical Physics developed more than a million different equations of state that satisfy the constraints set by data obtained from theoretical nuclear physics on the one hand, and by astronomical observations on the other. When evaluating the equations of state, the working group made a surprising discovery: “Light" neutron stars (with masses smaller than about 1.7 solar masses) seem to have a soft mantle and a stiff core, whereas “heavy" neutron stars (with masses larger than 1.7 solar masses) instead have a stiff mantle and a soft core. "This result is very interesting because it gives us a direct measure of how compressible the centre of neutron stars can be," says Prof. Luciano Rezzolla, "Neutron stars apparently behave a bit like chocolate pralines: light stars resemble those chocolates that have a hazelnut in their centre surrounded by soft chocolate, whereas heavy stars can be considered more like those chocolates where a hard layer contains a soft filling."
Crucial to this insight was the speed of sound, a study focus of Bachelor's student Sinan Altiparmak. This quantity measure describes how fast sound waves propagate within an object and depends on how stiff or soft matter is. Here on Earth, the speed of sound is used to explore the interior of the planet and discover oil deposits.
By modelling the equations of state, the physicists were also able to uncover other previously unexplained properties of neutron stars. For example, regardless of their mass, they very probably have a radius of only 12 km. Thus, they are just as large in diameter as Goethe University's hometown Frankfurt. Author Dr. Christian Ecker explains: "Our extensive numerical study not only allows us to make predictions for the radii and maximum masses of neutron stars, but also to set new limits on their deformability in binary systems, that is, how strongly they distort each other through their gravitational fields. These insights will become particularly important to pinpoint the unknown equation of state with future astronomical observations and detections of gravitational waves from merging stars."
So, while the exact structure and composition of matter inside neutron stars continues to remain a mystery, the wait until its discovery can certainly be sweetened with a chocolate or two.
Sinan Altiparmak, Christian Ecker, Luciano Rezzolla: On the Sound Speed in Neutron Stars. The Astrophysical Journal Letters (2022) https://iopscience.iop.org/article/10.3847/2041-8213/ac9b2aChristian Ecker & Luciano Rezzolla: A general, scale-independent description of the sound speed in neutron stars. The Astrophysical Journal Letters (2022) https://iopscience.iop.org/article/10.3847/2041-8213/ac8674
Image for download: https://www.puk.uni-frankfurt.de/128001606
Caption: The study of the sound speed has revealed that heavy neutron stars have a stiff mantle and a soft core, while light neutron stars have a soft mantle and a stiff core – much like different chocolate pralines (image: P. Kiefer/L. Rezzolla)
Editor: Dr. Phyllis Mania, Science Communication Officer, PR & Communication Office, Tel: +49 (0) 69 798-13001, Fax: +49 (0) 69 798-763 12531, email@example.com
Microbiologist Volker Müller receives funding from German Research Foundation’s Koselleck Programme
Acetic acid-producing bacteria (acetogens) are very interesting for the biotech industry: They fix the climate gas CO2 and at the same time produce not only acetic acid, but also substances such as ethanol or – after genetic modification – products such as acetone or bioplastics. For many years now, microbiologist Volker Müller from Goethe University has been researching how these bacteria extract energy from CO2 – and has done so very successfully. Now he wants to crack the last puzzle of this energy production. As part of the renowned Reinhart Koselleck Programme, the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) is now funding his project as a particularly innovative and refreshingly risky project.
FRANKFURT. They live in the soil, in sediments of bodies of water and in other oxygen-free environments: Bacteria known as acetogenic bacteria or acetogens that produce acetic acid from carbon dioxide (CO2) and obtain energy through this fermentation process. Phylogenetically, acetogens are among the oldest species of bacteria on Earth, having evolved more than three billion years ago, when the Earth's atmosphere was still oxygen-free. In recent years, the team of microbiologist Professor Volker Müller has partially elucidated how CO2 reduction is coupled with energy production: Acetogens have two different respiratory chains with the help of which they produce the cellular energy currency ATP, either with the central respiratory enzyme "Rnf" or with "Ech". Usually, a bacterial species possesses only one of these two respiratory chain types.
However, in addition to the enzymes Rnf or Ech, some acetogens also possess cytochrome-containing enzymes, which are central to oxygen respiration in both bacteria and higher cells. Although cytochomes were discovered in acetogens more than 40 years ago, no one has yet been able to demonstrate that acetogens – for which contact with oxygen is lethal – actually use their cytochromes for a form of respiration.
Over the next five years, the team led by Professor Volker Müller wants to find out what function cytochromes have in acetogens. The microbiologist explains: "Thanks to our many years of work on acetogens, we have the best prerequisites for cracking the riddle. These are very exciting times for us. After all, the cytochrome, which is much more complex to produce in biosynthesis for the bacterial cell, could actually be part of a third, oxygen-independent form of respiration. Or it may have a completely different function, perhaps serving to detoxify molecular oxygen and keep the bacterium from dying from oxygen."
With their basic research, the scientists want to prepare the ground for biotechnological applications of acetogenic bacteria. Currently, for example, 90 percent of the more than 3 million tons of acetic acid produced worldwide annually is obtained from fossil oil or gas. Müller: "If you want to use genetically modified acetogens to produce non-natural compounds such as acetone or bioplastics, you will need to have a sound understanding of the complex, essential metabolic processes in the bacteria. This is because the bacteria require a lot of energy for the non-natural compounds, which the chemical reduction of CO2 provides only to a limited extent. That is why with our research, we hope to make an important contribution to understanding energy production in acetogens, thereby opening the door for more efficient applications."
Professor Volker Müller holds the Chair of Molecular Microbiology and Bioenergetics at Goethe University's Faculty of Biological Sciences. He received his PhD in Göttingen, was a postdoctoral researcher at Yale University, habilitated in microbiology in Göttingen, and held a C3 professorship in microbiology at LMU Munich before coming to Frankfurt in 2002. He gained worldwide recognition for his work on the metabolism of acetogenic bacteria. His projects are funded by the German Research Foundation DFG and he coordinated a European research consortium on the application of acetogenic bacteria in industry. Currently, his work on the physiology and application of acetogenic bacteria is funded by a prestigious ERC Advanced Grant. With almost 300 publications, Müller is one of the world's leading researchers in the field of metabolism of anaerobic bacteria and archaea.
Image for download: https://www.uni-frankfurt.de/128212374
Caption: Professor Volker Müller, Goethe University Frankfurt (Photo: Uwe Dettmar for Goethe University)
Acetogenic bacterium contains both Rnf and Ech enzymes (01/2020)
Isolation of the Rnf enzyme complex
Professor Volker Müller
Department of Molecular Microbiology & Bioenergetics
Institute for Molecular Biosciences
Goethe University Frankfurt
Tel.: +49 (0)69 798-29507
Goethe University announces second Klaus Heyne-Award for research in Romanticism
FRANKFURT. Goethe University's Klaus Heyne-Award for Research into German Romanticism, endowed with 15,000 euros, is bestowed every two years to young scholars from Germany and abroad who are in their qualification phase and have made an outstanding academic contribution to Romanticism research. Launched in 2021, the award is now being announced for the second time. Applicants are not restricted to one discipline, such as literary studies, but may come from other disciplines, such as art history, musicology, or philosophy.
The award and the associated prize money consist of two components: 5,000 euros will be awarded on a non-earmarked basis, while 10,000 euros will be made available to the recipient for the conception and organization of a conference on Romantic research.
Interested parties can submit their application documents until January 31, 2023. The award winner will be honored at a ceremony held at Goethe University on October 11, 2023.
The new science award is made possible by a generous bequest from pediatrician Prof. Dr. Klaus Heyne (1937-2017), whose particular passion was the art and literature of German Romanticism.
The first recipient of the new science award in 2021 was Dr. Joanna Raisbeck, a literary scholar teaching at Oxford, who was honored for the innovative achievement of her dissertation "Poetic Metaphysics in Karoline von Günderrode." In 2022, she received the Novalis Prize for the same work. With the help of the Heyne Award, Raisbeck recently hosted an international conference on “Romantic Materialities" at Goethe University. Thanks to the cooperation between the Heyne Award and the Freies Deutsches Hochstift – one of Germany's oldest cultural institutes and a non-profit research institution – she was also able to curate an exhibition of Karoline von Günderrode's manuscripts at the Deutsches Romantik-Museum, which is on view until mid-December.
Contact and further information:
Prof. Dr. Frederike Middelhoff (W1 professorship for Modern German Literature with a focus on Romantic Studies)
Editor: Pia Barth, Public Relations Officer, PR & Communications Office, Tel. + 49 (0)69 798 12481, Fax + 49 (0)69 798 763 12531, firstname.lastname@example.org