Press releases – June 2019

FRANKFURT. The non-invasive measurement of blood flow to the heart using magnetic resonance imaging (MRI) is on par with cardiac catheterization. This was the result of an international study published in the current issue of the New England Journal of Medicine and headed by researchers from Goethe University.

For patients with chest pain and presumably stable coronary heart disease (CHD), therapy depends primarily on how constricted the arteries that support the heart are (coronary arteries). This is often determined using an invasive procedure called cardiac catheterization. If necessary, the pressure in the coronary arteries is also measured. The combination of these methods is the currently the recognized standard for making therapy decisions. Cardiovascular magnetic resonance imaging (MRI) is an alternative for directly measuring the blood flow in the myocardium. 

In contrast to cardiac catheterization, MRI is non-invasive, works without ionising radiation, can be done in 40 minutes and delivers direct measurements of the blood flow to the heart. The team headed by Professor Eike Nagel, Director of the Institute for Experimental and Translational Cardio Vascular Imaging at Goethe University was able to demonstrate that MRI measurements are as safe to guide decision-making as the currently used invasive procedure. Within the international MR-INFORM study, they examined 918 patients with an indication for cardiac catheterization to see if decision-making by an MRI scan led to the same results as the current invasive method. 

Patients were randomly assigned to two groups. One group received the standard diagnostic investigation with cardiac catheterization and pressure measurement of the coronary arteries. The other had the 40 minute MRI scan of the heart to decide whether to send the patient on for invasive angiography. 

In each study arm, constricted coronary vessels were dilated when indicated by the examination. In the following year, the physicians documented how many patients died, suffered a heart attack or required a repeated vascular dilation. In addition, they recorded whether the heart symptoms continued. 

The result: in the group of patients examined by MRI, less than half required a diagnostic cardiac catheterization and fewer patients received a vascular dilation (36% vs 45 %). This means that with a fast and non-invasive MRI examination as the first test, both diagnostic and therapeutic cardiac catheterizations can be reduced. Importantly, the two groups did not differ in terms of continuing symptoms, the development of new symptoms, complications, or deaths. 

“This means that patients with stable chest pains who previously would have received cardiac catheterization can alternatively be examined with MRI," concludes Professor Eike Nagel. “The results for the patients are just as good, but an examination by MRI has many advantages: the procedure takes about 40 minutes, patients merely receive a small cannula in their arm and are not subject to radiation." The physician hopes that the less invasive method will now be used as a method of first choice, reducing the need for cardiac catheterizations. 

In contrast to Great Britain, where an MRI scan of the heart is paid for by the National Health Service (NHS), reimbursement is often difficult in Germany and usually has to be negotiated individually. In this regard, Nagel also hopes that the study will contribute to the acceptance of the non-invasive procedure and improve its availability. 

Financial support was provided primarily by the British National Institute of Health Research (NIHR) via the Biomedical Research Centre (BRC) at Guy's & St. Thomas' Hospital, the German Centre for Cardiovascular Research (DZHK) and the company Bayer AG Deutschland. 

A picture can be downloaded here: http://www.uni-frankfurt.de/78920068
Caption: Measuring blood flow in the myocardium with magnet resonance imaging (top). The dark area in the myocardium (arrows) shows a pronounced reduction of blood flow. The cardiac catheterization of the same patient (bottom) shows a clear constriction of the artery. Credit: Eike Nagel, Goethe University

Publication: Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease Eike Nagel, et al., N Engl J Med 2019;380:2418-28. DOI: 10.1056/NEJMoa1716734

Further information: Professor Eike Nagel, Institute for Experimental and Translational Cardiovascular Imaging, Faculty of Medicine, Niederrad Campus, Tel.: +49 151 4197 4195, eike.nagel@cardiac-imaging.org

FRANKFURT. Unlike flawless gems, fibrous diamonds often contain small saline inclusions. These give hints to scientists about the conditions under which diamonds are formed deep in the Earth's mantle. A research team including scientists from Goethe University solved the puzzle of the formation of these inclusions by simulating conditions of extreme heat and pressure in the laboratory. 

Diamonds are crystals of carbon that form deep in the Earth's mantle underneath the oldest continents, the cratons. They are transported to the surface of the earth in exotic magmas called kimberlites by explosive volcanic eruptions. Previous studies had always determined that diamonds include fluids containing sodium and potassium, but the origin of these fluids was unknown. 

“In order for these inclusions to form, parts of the Earth's oceanic crust and their sediment layer had to be submerged beneath the cratonic continents in what is known as a subduction zone. These zones are located at depths of over 110 kilometres at a pressure of over four gigapascals, or 40 thousand times the atmospheric pressure," explains Michael Förster, the first author of the study that was published in the scientific journal Science Advances. The submergence of the earth's crust has to happen quickly so that the diamond can form before the sediment starts to melt at temperatures over 800 degrees Celsius, and react with the cratonic mantle. 

For the high-pressure experiment in the laboratory, scientists from Sydney, Mainz and Frankfurt stacked marine sediment and peridotite (rocks from the Earth's mantle) in four-millimetre capsules and placed them under high pressure and extreme temperatures. At pressures of four to six gigapascals – corresponding to depths of 120 to 180 kilometres – small salt crystals formed from the reaction between the two layers. Their potassium to sodium ratio corresponded exactly to the saline fluid inclusions in diamonds. In experiments with less pressure, corresponding to depths of less than 110 kilometres, these salts were not present. Instead, potassium was absorbed from the recycled sediment by mica. 

“Unlike previous models that attributed the source of the salts to seawater, the sediments represent a plausible source of potassium," says the mineralogist Professor Horst Marschall from Goethe University. “The potassium concentration in seawater is too low to explain the saline inclusions in diamonds." Magnesium-rich carbonates, important components of the kimberlites, also came about as a by-product of the reaction.

Publication: Michael W. Förster, et al. Melting of sediments in the deep mantle produces saline fluid inclusions in diamonds, in Science Advances, Vol.5 No. 5, DOI: DOI: 10.1126/sciadv.aau2620; https://advances.sciencemag.org/content/5/5/eaau2620 

A picture may be downloaded here: http://www.uni-frankfurt.de/78861524
Caption: Prof. Horst Marschall in front of one of the high-pressure belt apparatus in the Institute for Geosciences used to simulate the formation of inclusions in diamonds.  Credit: Horst Marschall, Goethe University 

Further information: Professor Horst Marschall, Wilhelm Heraeus Professor for Deep-Earth Processes, Institute for Geosciences, Faculty 11, Riedberg Campus, phone: +49 69 798- 40124 , marschall@em.uni-frankfurt.de

FRANKFURT. Jürgen Habermas is the most important contemporary German philosopher and one of the most frequently cited intellectuals worldwide. He played a decisive role in shaping the political debates in the Federal Republic of Germany. On the occasion of his 90th birthday, Habermas will return to Goethe University, where he carried out his research and taught until his retirement. The programme includes a public lecture in German by Habermas with the title: 

“Noch einmal: Zum Verhältnis von Moralität und Sittlichkeit“ 
(Once more: on the relationship between morality and ethics)
On Wednesday, 19th June 2019 at 6:00 p.m.
In the Hörsaalzentrum (HZ 1) on Westend Campus at Goethe University,
Theodor-W.-Adorno-Platz 5, 60323 Frankfurt am Main. 

In his lecture, Jürgen Habermas takes up a central issue in the field of practical philosophy and one that plays a significant role in his work. Starting from the controversy between Kant and Hegel, he asks how the principles of moral and political autonomy behave with regard to the “ethical" reality of historically situated communities. He argues that the principles of justice have priority over the imperatives of social integration and from this draws conclusions for our present day. 

Jürgen Habermas will celebrate his birthday the day before (18th June), and will then come to Frankfurt following an invitation by Professor Rainer Forst and Professor Klaus Günther, speakers of the Cluster if Excellence “The Formation of Normative Orders" at Goethe University. The Leibniz research group at Goethe University “Transnational Justice", headed by Professor Forst, was also involved in organizing the lecture.

  Goethe University President Professor Birgitta Wolff said, “Jürgen Habermas is one of the most influential personalities of Goethe University and contemporary philosophy. His discourse theory also inspired the Cluster of Excellence 'The Formation of Normative Orders', which has led to further current research initiatives such as the Frankfurt contribution to the “Institute for Societal Cohesion'." 

Professor Rainer Forst, political philosopher, stated “It's is a great honour and pleasure for us to welcome Jürgen Habermas at Goethe University on the occasion of his birthday. His discourse theory has been paradigm shaping in the fields of philosophy, law, and the social sciences. No one considering the most urgent challenges of our day, such as global justice, religiously pluralistic societies, or questions of cosmopolitan democracy and state citizenship can bypass his work." 

Jürgen Habermas had three separate stays in Frankfurt, where in his own words he experienced “the most exciting times" of his “adult life". He worked as assistant at the Institute for Social Research with Theodor W. Adorno from 1956 to 1959. As successor to Max Horkheimer, he held the double chair for philosophy and sociology at Goethe University from 1964 to 1971. 

Following his time at the Max-Planck-Institut zur Erforschung der Lebensbedingungen der wissenschaftlich-technischen Welt (Max Planck Institute for the research of living conditions in scientific-technical world) in Starnberg, where he still lives today, he again followed a summons to Frankfurt despite attractive alternative offers from the U.S. and other places. Here, he carried out research and taught as professor for philosophy with a focus on social philosophy from 1983 until his retirement in 1994. 

The Gottfried Wilhelm Leibniz Prize is among the many awards and distinctions Jürgen Habermas has received over his lifetime. This is still the most important and best endowed national science prize and Habermas received it in 1986, the year it was first awarded by the German Research Foundation (DFG). He used the funds to establish a legal-philosophical research group the “AG Rechtstheorie" (Legal Theory Working Group). Rainer Forst and the legal scholar Klaus Günther were among its members. 

The lecture will be opened by Goethe University President Professor Birgitta Wolff, followed by welcoming words from Ayse Asar, State Secretary of the Hessian Ministry of Higher Education, Research and the Arts, and from Professor Rainer Forst. 

Media representatives and the interested public are warmly welcome to attend. The lecture will be in German. 

During an internal conference at Goethe University in the following days, former students and colleagues of Jürgen Habermas will discuss his work with him, in particular his new book to be published in the fall. 

Please note: The organisers regret that interview requests with Professor Habermas cannot be accommodated. 

Further information: Bernd Frye, Cluster of Excellence Press Officer, phone: -49 69 798-31411, bernd.frye@normativeorders.net; www.normativeorders.net/de

FRANKFURT. Professor Robert Tampé, Director of the Institute of Biochemistry at Goethe University, has been elected to the European Organization for Molecular Biology, EMBO. The specialist in immune research thus ranks at one of the best researchers in Europe and the world. 

“It's a special distinction for the whole team, who was able to illuminate fundamental aspects of the adaptive immune system," says Robert Tampé. “These discoveries will not only find their way into textbooks, but will also provide a variety of therapeutic approaches for combatting infectious diseases and cancer." 

Just last year, Tampé was awarded an “ERC Advanced Grant" by the European Research Council amounting to 2.5 million euros. This project is dedicated to the question of how certain viruses circumvent control by the immune system. It particularly looks at molecular transport mechanisms that carry fragments of invading viruses to the cell's surface where they attract the attention of the T-cells of the immune system. Knowing how viruses bypass this process promises progress in the field of infectious and autoimmune diseases as well as in cancer research. The Reinhard Koselleck project, with 1.5 million euros in funding from the German Research Foundation (DFG), also deals with the quality control and assembly by macromolecular complexes that trigger the immune system. 

Through the Koselleck program, the DFG enables outstanding researchers to pursue exceptionally innovative and higher-risk projects. Tampé and his team are investigating the organization of the antigen quality control locations both inside the cell and in the cell membrane. The challenge lies in decoding the structure and function of larger, differently assembled protein complexes which, moreover, rarely exist in intercellular membranes. 

Robert Tampé studied chemistry at the Technical University Darmstadt where he received his doctorate in biochemistry. As Max-Kade Fellow, he explored mechanistic aspects of antigen presentation at Stanford University. From 1992 to 1998, he headed a research group at the Max Planck Institute of Biochemistry in Martinsried and he was appointed as Assistant Professor in Biochemistry at the Technical University of Munich in 1996. From 1996 to 1998 he was DFG Heisenberg Fellow. Subsequently, he headed the Institute of Physiological Chemistry at the Faculty of Medicine of the University of Marburg. Since 2001, he has been the director of the Institute of Biochemistry at Goethe University. He also holds honorary visiting professorships at the University of Oxford and University of Kyoto. 

EMBO is an organization of more than 1800 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. 

Further information: Prof. Dr. Robert Tampé, Institute of Biochemistry, Riedberg Campus, Tel. +49 69 798-29475, tampe@em.uni-frankfurt.de

FRANKFURT. Microorganisms often assemble natural products similar to product assembly lines. Certain enzymes, non-ribosomal peptide synthetases (NRPS), play a key role in this process. Biotechnologists at Goethe University have now succeeded in changing these enzymes so that entirely new natural products, or even libraries of natural products, can be produced by microorganisms. 

Many important natural products such as antibiotics, immunosuppressants, or anti-cancer drugs are produced by microorganisms. These natural products are often small peptides, which in several cases are too complex for a chemical synthesis in the laboratory. In the microbial producers of these drugs, the drugs are generated with the help of the NRPS enzymes in a manner similar to a modern automobile factory: at each station, additional parts are added to the basic structure until finally a complete automobile leaves the factory. In the case of NRPS, a specific amino acid is incorporated and processed at each station (module) so that in the end, peptides emerge that can be linear, cyclic or otherwise modified, and which can also carry unusual amino acids. 

Although the basic principles of NRPS have been known for a long time, it was previously hardly possible to modify these enzymes in an easy and efficient way that also allows the complete assembly of fully artificial enzymes leading to new-to-nature peptides. While in the past NRPS modification usually led to a dramatic drop in the production titre of the desired modified peptides, the Molecular Biotechnology research group of Professor Helge Bode already published a new method in 2018 that avoided this drawback. The group has now further optimized this method allowing the easy production of new peptides in excellent yield. 

“We use fragments of natural NRPS systems from different bacteria as building blocks that we connect to each other using specific assembly points we have identified," Andreas Tietze and Janik Kranz explain the research approach they developed as part of a larger team in the Bode group. “The yields are comparable to the natural production of the non-modified natural products and the new methods also enable the simple production of peptide libraries, which was not possible before". 

The method is so well established, beginners can use it to produce new peptides after a short training period. But to get to this point was a long way. “Following the first promising experiments by Kenan, my PhD student at the time, we worked for a long time on the project with a major part of my group until we were certain that our method fulfilled the requirements of a robust and easily reproducible engineering method," Bode states. “Thanks to the LOEWE priority programmes MegaSyn and Translational Biodiversity Genomics, we had the necessary personnel and financial support, and could concentrate completely on the project." 

The next step is to modify the first clinically relevant drugs with this method and produce them in microorganisms applying biotechnology methods. The conditions for this are good - Bode was only recently awarded one of the renowned ERC Advanced Grants from the European Research Council in order to further optimize the methods over the next five years. 

Publication: Kenan A. J. Bozhüyük, Annabell Linck, Andreas Tietze, Janik Kranz, Frank Wesche, Sarah Nowak, Florian Fleischhacker, Yan-Ni Shi, Peter Grün, Helge B. Bode: Modification and de novo design of non-ribosomal peptide synthetases (NRPS) using specific assembly points within condensation domains, Nature Chemistry, https://www.nature.com/articles/s41557-019-0276-z; DOI: https://doi.org/10.1038/s41557-019-0276-z 

An image can be downloaded here: http://www.uni-frankfurt.de/78678421 
Caption: From left to right: Dr. Yan-Ni Shi, Prof. Helge Bode, Janik Kranz, Peter Grün und Andreas Tietze.. Credit: Jürgen Lecher, Goethe-Universität. 

Further information: Professor Helge B. Bode, Molecular Biotechnology, Faculty of Biological Sciences, Riedberg Campus, Tel.: +49 69 798-29557, H.Bode@bio.uni-frankfurt.de.