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International research team shows long-range effect of bacterial metabolites for the first time
Bacteria in the intestine pack a wide spectrum of their biomolecules into small capsules. These are transported via the bloodstream to various organs in the body and even absorbed and processed by nerve cells in the brain. This has now been shown for the first time by a team of researchers from Goethe University, FAU (University of Erlangen-Nuremberg) and the University of California in San Francisco. The newly established research method will help to better understand the influence of intestinal bacteria on diseases and could support the development of innovative forms of drug or vaccine delivery.
FRANKFURT. In the human body, bacteria are in the majority: According to estimates, there are 1.3 bacterial cells for each human cell. Our bacteria are correspondingly superior to us in their genetic diversity. All intestinal bacteria together – the intestine's microbiome – have 150 times as many genes as humans. The intestinal bacteria's metabolic products have a variety of effects on our body: For example, they train our immune cells and contribute to their maturation, they control metabolic processes in the body and how often intestinal mucosa cells renew themselves. It is highly probable that changes in the microbiome's composition contribute to the development and course of diseases, e.g. neurological disorders or cancer.
The bacterial metabolites act on the cells of the intestinal mucosa via direct contact. However, how such bacterial substances travel to peripheral organs, such as the liver, kidney or brain, had not yet been explained. It was assumed that small capsules (membrane vesicles), released by bacteria into their environment during normal growth or as a reaction to stress and filled with bacterial lipids, proteins or also hereditary RNA molecules, were the means of transport.
An international research team led by Dr Stefan Momma from the Neuroscience Centre of Goethe University, Professor Claudia Günther from FAU (University of Erlangen-Nuremberg) and Professor Robert Raffai from the University of California has now investigated in mice how bacteria distribute their metabolic products in such vesicles. For this purpose, the researchers colonized the intestines of mice with E. coli bacteria, which produced a specific type of gene scissors (Cre) and released these into their environment via vesicles. The mice cells contained a gene for a red fluorescent protein, which could be activated by the Cre gene scissors (Cre/LoxP system).
The result: In the subsequent examination of the mouse tissue, the bacterial vesicles had been absorbed by individual cells in the intestine, liver, spleen, heart and kidneys as well as by immune cells. Consequently, functional Cre contained in the vesicles could enter the cells and lead to the expression of the red marker protein. Even individual nerve cells in the brain glowed red. Stefan Momma: “Particularly impressive is the fact that the bacteria's vesicles can also overcome the blood-brain barrier and in this way enter the brain – which is otherwise more or less hermetically sealed. And that the bioactive bacterial substances were absorbed by stem cells in the intestinal mucosa shows us that intestinal bacteria can possibly even permanently change its properties."
The fluorescence images indicate, says Momma, that the vesicles were probably distributed throughout the body via the bloodstream. “The further study of these communication pathways from the bacterial kingdom to individual mammalian cells will not only improve our understanding of conditions such as autoimmune diseases or cancer, in which the microbiome quite obviously plays a significant role. Such vesicles are also extremely interesting as a new method to deliver drugs or develop vaccines, or as biomarkers that point to a pathological change in the microbiome."
Publication: Miriam Bittel, Patrick Reichert, Ilann Sarfati, Anja Dressel, Stefanie Leikam, Stefan Uderhardt, Iris Stolzer, Tuan Anh Phu, Martin Ng, Ngan K. Vu, Stefan Tenzer, Ute Distler, Stefan Wirtz, Veit Rothhammer, Markus F. Neurath, Robert L. Raffai, Claudia Günther, Stefan Momma: Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo. J Extracell Vesicles 2021 Oct;10(12):e12159 https://onlinelibrary.wiley.com/doi/10.1002/jev2.12159?af=R
Pictures to download: https://www.uni-frankfurt.de/108079209
Caption: In the brain of the transgenic mouse, two nerve cells glow red because they have absorbed membrane vesicles containing functional protein from intestinal bacteria. Blue: nuclei of the other cells in the brain tissue. (Photo: Stefan Momma)
Dr Stefan Momma
Goethe University Frankfurt, Germany
Institute of Neurology (Edinger Institute)
Tel.: +49 (0) 69 6301-84158
Researchers have identified a potential new treatment that suppresses the replication of SARS-CoV-2, the coronavirus that causes Covid-19. In order to multiply, all viruses, including coronaviruses, infect cells and reprogramme them to produce novel viruses. The research revealed that cells infected with SARS-CoV-2 can only produce novel coronaviruses when their metabolic pentose phosphate pathway is activated.
When applying the drug benfooxythiamine, an inhibitor of this pathway, SARS-CoV-2 replication was suppressed and infected cells did not produce coronaviruses.
The research from the University of Kent's School of Biosciences and the Institute of Medical Virology at Goethe-University, Frankfurt am Main, found the drug also increased the antiviral activity of '2-deoxy-D-glucose'; a drug which modifies the host cell's metabolism to reduce virus multiplication.
This shows that pentose phosphate pathway inhibitors like benfooxythiamine are a potential new treatment option for COVID-19, both on their own and in combination with other treatments.
Additionally, Benfooxythiamin's antiviral mechanism differs from that of other COVID-19 drugs such as remdesivir and molnupiravir. Therefore, viruses resistant to these may be sensitive to benfooxythiamin.
Professor Martin Michaelis, University of Kent, said: 'This is a breakthrough in the research of COVID-19 treatment. Since resistance development is a big problem in the treatment of viral diseases, having therapies that use different targets is very important and provides further hope for developing the most effective treatments for COVID-19.'
Professor Jindrich Cinatl, Goethe-University Frankfurt, said: 'Targeting virus-induced changes in the host cell metabolism is an attractive way to interfere specifically with the virus replication process.'
Publication: Denisa Bojkova, Rui Costa, Philipp Reus, Marco Bechtel, Mark-Christian Jaboreck, Ruth Olmer, Ulrich Martin, Sandra Ciesek, Martin Michaelis, Jindrich Cinatl, Jr.: Targeting the pentose phosphate pathway for SARS-CoV-2 therapy. In: Metabolites 2021, 11(10), 699; https://doi.org/10.3390/metabo11100699
information: Cell culture model: several compounds
stop SARS-CoV-2 virus. Frankfurt researchers discover potential targets for
Following the decision by the Joint Science Conference on 22 October, the new “NHC South-West Alliance”, to which Goethe University also belongs, will receive grants totalling € 40 million from the national and regional governments.
FRANKFURT. As of 22 October, Goethe University is part of the National High-Performance Computing Alliance. The “Joint Science Conference" (GWK) announced its decision today in Bonn. The “NHC South-West Alliance" has been approved and will receive € 124 million over a period of ten years (€ 40 million of which will come from Joint Science Conference funds). The alliance covers three federal states, Hessen, Rhineland-Palatinate and Saarland, with facilities in Frankfurt (Goethe University), Mainz (Johannes Gutenberg University Mainz (JMU)), Kaiserslautern (Technical University of Kaiserslautern) and Saarbrücken (Saarland University). € 45 million are earmarked for the future development of high-performance computing at Goethe University, whose own contribution is € 30 million.
With this decision, the Joint Science Conference is also underlining Goethe University's excellent performance in the area of green IT, for which the Frankfurt team led by Professor Volker Lindenstruth is responsible. Coming in 1st, 2nd and 8th place, supercomputers designed by Lindenstruth have achieved exceptionally good rankings in recent years in the biannual “Green 500" world rankings, on a global scale too. With the grant from the Joint Science Conference, Hessen now has two National High-Performance Computing (NHC) centres.
Professor Enrico Schleiff, President of Goethe University, expressed his delight at the positive decision announced by the Joint Science Conference of the national and regional governments: “This is tremendous acknowledgement of the great and continuous efforts we've been making for over ten years in the development and realisation of energy-saving supercomputers. I thank Volker Lindenstruth's team for their persevering work on the further development of this trailblazing technology, which is meanwhile also a bestseller and in demand worldwide. I would also like to thank our Minister of Science, Angela Dorn, for giving our application her sustained support. With the appointment of further outstanding professors in this field, we will further strengthen this research priority in the coming years and, together with our partners in Rhineland-Palatinate and Saarland, set important new trends in the further technological development of energy-saving computing systems."
Angela Dorn, Hessian Minister of Science, commended the role of Goethe University in the new alliance: “An alliance makes us stronger because the universities each contribute their own strengths. Professor Volker Lindenstruth and his team at Goethe University have, for example, developed technologies for energy-saving high-performance computers, and the Hessian Ministry of Higher Education, Research, Science and the Arts (HMWK) has supported this development on a large scale for over 10 years as part of the LOEWE Initiative. I'm pleased and proud that this support has yielded such a sustainable return – above all also for the protection of our environment and the reduction of CO2 emissions. Many a data centre today could heat a small town with its waste heat. In the fight against catastrophic climate change, we must make use of every opportunity to reduce energy consumption – and green IT makes an important contribution here, also in the area of high-performance computing."
Professor Volker Lindenstruth, Professor for High-Performance Computing Architecture at Goethe University and Chairman of the Board of the Frankfurt Institute for Advanced Studies (FIAS), sees Goethe University's inclusion in the National High-Performance Computing Alliance as an important milestone for further research in Frankfurt in the area of green IT: “As part of the National High-Performance Computing Alliance, it's now even more possible to use the fruits of our research for the benefit of the general public and for more intensive research work. For example, we've accomplished remarkable progress at Goethe University over the last ten years as far as increasing the efficiency of scientific software is concerned. As a result, the same scientific results can be produced with much less energy consumption. Hundredfold increases in computing speed have been achieved for many applications, making even very complex problems calculable for the first time ever. For example, the highly efficient algorithms developed at Goethe University were and are used both in particle physics at CERN as well as at FAIR at the GSI Helmholtz Centre for Heavy Ion Research."
In addition to the four new centres mentioned above, to date there are also NHC centres in Aachen, Berlin, Dresden, Erlangen-Nuremberg, Göttingen, Karlsruhe, Paderborn and Darmstadt, meaning that from now on all three locations of the alliance of Rhine-Main Universities (RMU) are also part of the alliance.
High-performance supercomputers are becoming increasingly important in science and research. In view of increasingly complex and large volumes of data, researchers in the widest variety of disciplines are more dependent than ever on high-performance computers. Today, more and more research questions, for example in medicine, physics or chemistry, can only be answered by means of large-scale computing capacities and intelligent applications. That is the reason behind the decision by Germany's national and regional governments in 2018 to establish a nationwide National High-Performance Computing Alliance (NHC) in order to bundle and further develop the existing strengths of high-performance computing centres within a national network. The establishment of a coordinated alliance is a response to the growing demand for high-performance computing by enabling researchers at universities to access the computing capacity they need for their research across Germany and in line with their needs, regardless of their respective locations. Through the National High-Performance Computing Alliance, the technical and methodological strengths of high-performance computing centres will also be further upgraded and better aligned. At the same time, the aim is to introduce a greater number of researchers to high-performance computing through training and continuing education at the nine NHC centres, to enhance the skills of high-performance computing system users and to foster young talent in order to fully utilise the potential of high-performance computers and to strengthen Germany as a location for research and innovation. A total of € 625 million is earmarked for the National High-Performance Computing Alliance over the ten-year funding period.
Editor: Dr. Olaf Kaltenborn, PR & Communication Department, Tel: +49 (0) 69 798-13035, Fax: +49 (0) 69 798-763 12531, email@example.com
Inaugural lecture of Prof. Dr. Flurina Schneider at Goethe University
FRANKFURT. In the winter semester of 2021/22, Flurina Schneider, scientific director of ISOE – Institute for Social-Ecological Research, will take up her professorship for Social Ecology and Transdisciplinarity at Goethe University Frankfurt. The joint professorship of the independent research institute ISOE and the university is the first with this particular focus in Germany. The inaugural lecture “Research for sustainable development – from knowledge processes and options for action" will take place on October 20, 2021 on the Riedberg campus.
Social ecology is still a comparatively young scientific field that has proven central to environmental and sustainability research in recent decades and is now for the first time entering university teaching with a professorship. Social ecology examines the relationships between society and nature and poses the question of how these relationships can be made more sustainable. Particular importance is attached to the role of knowledge processes. “In the search for science-based solutions to challenges such as climate change or biodiversity loss, social ecology, with its transdisciplinary approach, facilitates joint learning processes between science and society. That is why it plays a key role in sustainability research", says Flurina Schneider, who will give her inaugural lecture at Goethe University Frankfurt on October 20, 2021.
Cooperation between ISOE and Goethe University in research, teaching and transfer
In Germany, social ecology was mainly developed by ISOE, which developed this transdisciplinary field of science in terms of their research program. “I am very pleased to take up the first professorship in this important field of science in Germany at Goethe University Frankfurt," says ISOE's scientific director Flurina Schneider. With the joint professorship in Social Ecology and Transdisciplinarity, which was created on the initiative of the independent research institute in Frankfurt and which is part of the Faculty of Biological Sciences, ISOE is intensifying its long-standing cooperation with Goethe University in research, teaching and transfer. Since 2008, ISOE's scientists have been teaching theoretical concepts, methods, and empirical applications of social-ecological research as part of the environmental master's program at Goethe University.
Anchoring the educational mandate for sustainable development in academic teaching
With the professorship, ISOE and Goethe University are also responding to the growing demand in the field of sustainability research and related research methods. “As a university, we take the mandate to anchor education for sustainable development in our courses of study very seriously," says Enrico Schleiff, president of Goethe University Frankfurt. “We are therefore extremely pleased to have Flurina Schneider, an internationally renowned expert in Transdisciplinary Sustainability Research, as a professor for this chair, which is unique in Germany. Her expertise in scientific principles and methods with respect to socio-ecological transformation processes and sustainable development is not only a great asset for our range of courses, but also for the university as a whole: sustainability as the preservation of natural life-support systems and climate protection is a matter close to our hearts in research, teaching and administration."
A professor with wide-ranging expertise in environmental and sustainability research
The Swiss sustainability researcher Flurina Schneider has been scientific director of ISOE since April 1, 2021. She is the successor of Thomas Jahn, who co-founded ISOE in 1989. Schneider completed her habilitation in 2016 on the topic of transdisciplinary and transformative research for sustainable governance of natural resources with a view to intra- and intergenerational justice at the University of Bern, where she had been employed as a researcher and head of the Land Resources Research Cluster since 2010. Her scientific activities span broad areas of environmental and sustainability research: from soil-conserving farming systems and quality assurance of eco-products to equity in land and water governance and research projects explicitly addressing the role of transdisciplinary knowledge production in sustainability transformations.
The importance of knowledge in sustainability processes
The role of knowledge in sustainability transformations is Flurina Schneider's key research and teaching priority. She will address this topic also in her inaugural lecture. “It is crucial to understand the mechanisms by which scientific knowledge translates into societal action and what types of knowledges are needed for social-ecological transformations to actually succeed," says Schneider. She will also focus on issues of environmental justice between the generations, as well as between countries in the global North and South. “I'm really looking forward to giving students access to all the complex issues and challenges of sustainability research."
Inaugural lecture of Prof. Dr. Flurina
“Research for sustainable development – from knowledge processes and options for action"
Date: October 20, 2021, time: start at 1 pm, location: Lecture Hall 2 of the Otto Stern Center on the Riedberg Campus of Goethe University Frankfurt.
Prof. Dr. Flurina Schneider
Tel. +49 69 7076919-0
Tel. +49 69 7076919-51
Potential applications as nano semiconductor materials
Chemists at Goethe University Frankfurt have developed two new classes of materials in the field of nanomaterials and investigated them together with their cooperation partners at the University of Bonn: for the first time, they have succeeded in producing a nano sphere of silicon atoms and a building block for a diamond-like crystal of the semiconductor elements silicon and germanium. The two new classes of materials have potential applications in the miniaturisation of computer chips, in high-resolution screens for smartphones, and in solar cells and light-emitting diodes with the highest levels of efficiency.
FRANKFURT. The latest generations of computer chips are only a few nanometres in size and are becoming ever more energy-saving and powerful as a result of progressive miniaturisation. Since the etching processes traditionally used in chip production are increasingly reaching their limits, the development of new, nanostructured semiconductor materials is essential. Such nano semiconductors also play a central role in converting electricity into light and vice versa.
A team at Goethe University Frankfurt led by Matthias Wagner has now succeeded in synthesising molecular nano "spheres" made of 20 silicon atoms, so-called silafulleranes. The second new class of materials are crystal building blocks made of 10 silicon and germanium atoms that have a diamond-like structure. Decisive insights into the electronic structures of the new compounds were provided by computer-based theoretical analyses from Stefan Grimme's research group in Bonn.
The 20 silicon atoms of silafullerane form a dodecahedron, a body composed of regular pentagons. It encapsulates a chloride ion. A hydrogen atom protrudes outward at each silicon corner of the body. Doctoral student Marcel Bamberg, who synthesised the molecule, explains: "Our silafullerane is the long-sought progenitor of this new class of substances. The hydrogen atoms can easily be replaced with functional groups, thus giving the silafullerane different properties." Bonn quantum chemist Markus Bursch adds: "We support the targeted generation of potentially useful properties with theoretical predictions of their resulting effects."
The silicon-germanium adamantane represents the building block of a mixed silicon-germanium alloy. Benedikt Köstler, who is developing the compounds as part of his doctoral thesis, says: "Recent studies have shown that silicon-germanium alloys are superior to pure silicon semiconductors in important application areas. However, the production of such alloys is very difficult and you often get mixtures of different compositions. We have succeeded in developing a simple synthesis path for the basic building block of silicon-germanium alloys. Our silicon-germanium adamantane therefore enables the investigation of important chemical and physical properties of silicon-germanium alloys on the molecular model. We also want to use it in the future to produce silicon-germanium alloys with faultless crystal structures."
Carbon, which is chemically very similar to the elements silicon and germanium, occurs in comparable forms to the two new classes of substances: Hollow spheres of carbon atoms ("fullerenes") correspond to silafulleranes, and diamonds consisting of carbon are composed of adamantane subunits. Among other things, fullerenes increase the efficiency of organic solar cells, could make the batteries of electric cars safer, and promise progress in high-temperature superconductivity. Nanodiamonds also have a wide range of applications, from pharmaceuticals to catalysis research.
Against this background, the researchers in Frankfurt and Bonn are excited to see in which fields their silafulleranes and silicon-germanium adamantanes will become established. Matthias Wagner says: "It is already possible to generate light in all colours of the visible spectrum with nanostructured silicon and germanium in the form of quantum dots, and this is being tested for computer and mobile phone displays, as well as in telecommunications. Apart from the chemical-technical potential, I am personally fascinated by the high symmetry of our compounds: For example, our silafullerane is one of the five Platonic solids and possesses a timeless beauty."
(1) Marcel Bamberg, Markus Bursch, Andreas Hansen, Matthias Brandl, Gabriele Sentis, Lukas Kunze, Michael Bolte, Hans-Wolfram Lerner, Stefan Grimme, Matthias Wagner: [Cl@Si20H20]−: Parent Siladodecahedrane with Endohedral Chloride Ion. J. Am. Chem. Soc. 2021, 143, 10865–10871 https://doi.org/10.1021/jacs.1c05598
(2) Benedikt Köstler, Michael Bolte, Hans-Wolfram Lerner, Matthias Wagner: Selective One-Pot Syntheses of Mixed Silicon-Germanium Heteroadamantane Clusters. Chem. Eur. J. https://doi.org/10.1002/chem.202102732 Images for download: https://www.uni-frankfurt.de/105049499
(1) The silicon sphere [Cl@Si20H20]−, synthesised for the first time by chemists from Goethe University Frankfurt, promises new applications in semiconductor technology. Blue: silicon, green: chloride ion, grey: hydrogen. Graphic: Goethe University Frankfurt
(2) Building block for silicon-germanium alloys: A section of the silicon-germanium adamantane synthesised in Frankfurt (shown here without substituents). Blue: silicon, magenta: germanium. Graphic: Goethe University Frankfurt
Professor Matthias Wagner
Institute for Inorganic and Analytical Chemistry
Goethe University Frankfurt
Tel.: +49 69 798 29156