PROXIDRUGS project led by Goethe University included in concept phase of “Clusters4Future” programme – search for novel active components for therapeutic solutions
FRANKFURT. PROXIDRUGS, the regional network led by Goethe University, aims at developing active molecules for selective intervention, opening new therapeutic avenues. Within the “Clusters4Future" ideas competition, the Federal Ministry of Education and Research has now selected the project for funding in the concept phase – as one of 16 finalists out of 137 proposals submitted.
“The body has developed an ingenious mechanism for disposing of superfluous or harmful proteins. We wish to seize this to break down disease-relevant proteins," says PROXIDRUGS coordinator Professor Ivan Đikić from the Institute of Biochemistry II at Goethe University, explaining the project's rationale. Developing better therapies for diseases such as cancer, heart or inflammatory disease is the goal of the alliance of biochemists, chemists, clinicians and pharmacists from Goethe University, the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) and TU Darmstadt.
The Federal Ministry of Education and Research will support the project with funds of up to € 250,000 during the six-month concept phase starting in May. If the alliance then qualifies for the implementation phase, up to € 5 million will be available per year for PROXIDRUGS. With this funding scheme, the Ministry wants to turn scientific hotspots into powerful regional innovation networks. “Goethe University at the heart of the Rhine-Main region, a top location unique in Germany, bundles academic and industrial expertise for the development of innovative therapeutic concepts," says Professor Simone Fulda, the University's Vice-President, praising the consortium's approach, which is based on reprogramming of the cell's own systems.
Proteins destined for degradation are usually marked in an enzymatic reaction with the small protein ubiquitin. The cell's “shredder", the proteasome, recognizes this signal and breaks the respective protein down into its individual components, which are then recycled. At the focus of PROXIDRUGS is a novel class of drugs acting through a proximity-based mechanism: The corresponding molecules exhibit two functional units – one for the selective binding of the respective target protein and a second one to dock onto the required enzyme. In this way, any unwanted protein that has a suitable binding pocket can in principle be marked with ubiquitin and flagged for degradation.
First molecules based on this principle, called PROTACs (Proteolysis Targeting Chimeric Molecules), already exist. A major advantage is their high specificity and catalytic mode of action – meaning that each molecule can carry out multiple reactions, such that only a small amount of active drug is needed. First trials with PROTACs in prostate and breast cancer are currently underway. The researchers in the PROXIDRUGS alliance now want to create new molecules in this very promising class of drugs, e.g. for diseases that until now cannot be treated with small molecules.
One of the aims of the PROXIDRUGS alliance of Goethe University, TU Darmstadt and the Fraunhofer IME is to bundle existing expertise in basic and clinical research, in pharmaceutical and biotech companies in the Rhine-Main region within one network. “Translation of our results to the clinic will be challenging," says Đikić. “However, thanks to close collaboration with regional companies, which have already shown great interest in the project, and the involvement of University Hospital Frankfurt, I'm confident that we'll master this challenge."
Further information: www.bmbf.de/zukunftscluster
An image and the logo can be downloaded under: http://www.uni-frankfurt.de/85772916
Image Caption: Diagram of PROTACs' mode of action. A PROTAC is bifunctional and comprises a ligand (L, green) for the enzyme E3 ligase and a binding domain (L, red) for the target protein, connected via a short linker region (black). (Graphik: IBC2/GU)
Further information: Dr Kerstin Koch, Institute of Biochemistry II, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany, Tel.: +49(0)69-6301-84250, Email: email@example.com
Patenting and commercialization crown ten years’ development work based on the “Green IT” approach of Professor Volker Lindenstruth of Goethe University and the GSI Helmholtz Centre for Heavy Ion Research
FRANKFURT. By 2030, data centres could be responsible for 13 percent of worldwide power consumption. In Frankfurt, the global network node with the highest data volume, data centres today already consume 20 percent of all local electricity – and this figure is rising. A large part of it is used for cooling power. Already today, the waste heat from single large-scale data centres could be used to heat up to 10,000 households.
An answer to this global challenge comes from Hessen. To be specific, it comes from Goethe University and the GSI Helmholtz Centre for Heavy Ion Research, which were recently granted a European patent for their concept for an energy-efficient cooling structure for data centres. This patent now paves the way for the commercialization of the pioneering technology developed by Professor Volker Lindenstruth, Professor Horst Stöcker and Alexander Hauser of e3c. Together with parallel patents outside Europe, the invention can now be put to economic use throughout the world. The team has already received enquiries from various countries for the construction of such data centres.
The data centre is thus becoming an important export commodity “Made in Hessen". This success is also thanks to Innovectis, Goethe University's own transfer agency, and its managing director Dr Martin Raditsch, the driving force behind the invention's commercialization, as well as Dr Tobias Engert, head of the GSI's Technology Transfer Department. The successful commercialization of the patents is a perfect example of collaboration between a university and a major research facility in Hessen.
NDC Data Centers GmbH, a Munich-based company, has obtained the rights to market the green technology in data centre construction projects around the globe and is thus also making a major contribution to the careful handling of our energy resources against the backdrop of global digitalization.
The basis for these activities is the visionary concept of a significantly optimized cooling system for data centres with the highest possible level of energy efficiency, which was developed by Volker Lindenstruth, Professor for High-Performance Computing Architecture at Goethe University and former head of the Scientific IT Department at GSI. On the basis of his concept, data centres and commercial IT systems can today be operated with up to 50 percent less primary energy consumption in comparison to conventional data centres.
The technology has been in use for years and is being continuously improved: The first data centre of this type was Goethe University's own, which was set at in the Infraserv industrial park. Another very data centre, the Green IT Cube, was built by the GSI Helmholtz Centre in Darmstadt and financed from funds provided by the German federal government and the Federal State of Hessen via Helmholtz expansion investments. The concept enables the realization and particularly efficient operation of data centres for large-scale research facilities such as FAIR (Facility for Antiproton and Ion Research), which is currently being set up at the GSI. Later, the Green IT Cube will be the central data centre for FAIR, one of the largest projects worldwide in support of research. Moreover, the waste heat from the servers in the Green IT Cube is already being used today to heat a modern office and canteen building on the GSI campus.
Apart from the high energy savings associated with the use of this new technology, the construction of such data centres is also extraordinarily cost-efficient, thus minimizing procurement and operating costs: An expedient coupling of ecology and economy.
Lindenstruth's supercomputers have received several awards for their energy-efficient concept in recent years. At the end of 2014, one of his computers ranked first place in the global listing of the most energy-efficient supercomputers, thanks to its greatly optimized computer architecture.
Goethe University's success in the area of green IT is also spurring on its current application, together with Mainz, Kaiserslautern and Saarbrücken, to host one of the new National High-Performance Computing Centres. Thanks to the optimized computer architecture based on the Hessian green IT approach, considerably more computing power could be made available to users at the same cost. Goethe University would therefore be an ideal location for one of the new centres.
Views on the green supercomputer technology:
Angela Dorn, Hessen's Minister of Science, says: “My sincere congratulations to Professor Lindenstruth and his team. I'm especially pleased that this success has been accomplished in a field close to my heart: The energy turnaround to which green IT can make a very important contribution. I'm also very happy that we as the Federal State of Hessen have contributed to this success. The first supercomputer in which Professor Lindenstruth used his energy-saving technology was the LOEWE-CSC at Goethe University's data centre in the Infraserv industrial park. Hessen's Ministry of Science supported this investment with a total of almost € 2 million in the shape of both direct funding as well as from the LOEWE programme. We're therefore today harvesting together the fruits of this funding and the LOEWE programme launched in 2008."
Professor Birgitta Wolff, President of Goethe University, says: “Just as in Goethe's days it made no sense to harness more and more horses in front of a stagecoach in order to increase the speed, so today we are facing a fundamental paradigm shift in IT. Back then, the railroad was the answer to the problem of speed. Today, the smart IT sector has a huge sustainability and energy problem. To satisfy its enormous hunger for data, our IT-based society requires new energy concepts for supercomputers that drastically reduce power consumption. Volker Lindenstruth from Goethe University has developed such a solution. Its successful patenting with the support of our subsidiary Innovectis is a major step in the right direction: The dissemination and commercialization of this truly smart technology."
Professor Volker Lindenstruth, Professor for High-Performance Computing Architecture at Goethe University, says: “Our successful patent registration is a milestone for the further global commercialization of our “Green IT" approach. We've already received enquiries for it from various regions worldwide. This gives our work a further boost, the more so since with NDC we now have a strong business partner at our side to help with the practical steps."
Professor Karlheinz Langanke, Research Director of the GSI Helmholtz Centre for Heavy Ion Research and FAIR – Facility for Antiproton and Ion Research in Europe, says: “The Green IT Cube high-performance computing centre at the GSI Helmholtz Centre is an outstanding example of how practical and usable know-how and developments evolve out of basic research. The Green IT Cube was developed for enormous volumes of measurement data from scientific research: It provides the highest computing capacities required and is at the same time extraordinarily energy-efficient and space-saving."
Markus Bodenmeier, NDC co-founder and partner: “With the help of the innovations created by Professor Volker Lindenstruth from Goethe University and by the GSI, NDC Data Centers GmbH builds the most energy-efficient and resource-friendly data centres. In so doing, we can guarantee over the long term the benefits offered by the exponential growth of digitalization. We're in keeping here with the current trend – all major cloud operators are at present keeping a very close eye on the impact of their activities on the environment."
Other statements by experts involved:
Dr Martin Raditsch, Managing Director of Innovectis GmbH, a subsidiary of Goethe University explains: “The application in practice of this technology is a very nice example of how results from basic research at the University and their transfer lead to technological solutions for societal challenges. Through our technology, the advancing digitalization of industry and society can be accomplished in a far more energy-saving way."
Dr Tobias Engert, Director of the Technology Transfer Department at the GSI, is very pleased about the invention's success: “The cooling concept of the Green IT Cube at the GSI is based on an innovative idea for the reduction of energy costs, and together with Innovectis we've now been able to successfully market it to NDC. Equipped with an innovative cooling system, the Green IT Cube meets the high requirements of optimum energy efficiency coupled with the highest possible computing power, and it will later become the central data centre for the new accelerator FAIR – Facility for Antiproton an Ion Research. The commercialization of the patents is certainly one of the most important examples of technology transfer from the GSI into industry." His colleague Michael Geier, Director of the Patents Department, adds: “The sale of the patents to NDC corroborates how important it is to protect new technical solutions developed at research facilities such as the GSI through patents. Such patents are a deciding factor for technology transfer into industry, through which income is generated that then flows back into research."
High-resolution 3D microscopy shows how plants adapt flexibly to their surroundings
FRANKFURT. Plants use their roots to search for water. While the main root digs downwards, a large number of fine lateral roots explore the soil on all sides. As researchers from Nottingham, Heidelberg and Goethe University of Frankfurt report in the current issue of “Nature Plants", the lateral roots already “know" very early on where they can find water.
For his experiment, Daniel von Wangenheim, a former doctoral researcher in Professor Ernst Stelzer's Laboratory for Physical Biology and most lately a postdoc at Malcolm Bennett's, mounted thale cress roots along their length in a nutrient solution. They were, however, not completely immersed and their upper side left exposed to the air. He then observed with the help of a high-resolution 3D microscope how the roots branched out.
To his surprise, he discovered that almost as many lateral roots formed on the air side as on the side in contact with the nutrient solution. As he continued to follow the growth of the roots with each cell division in the microscope, it became evident that the new cells drive the tip of the root in the direction of water from the very outset, meaning that if a lateral root had formed on the air side, it grew in the direction of the agar plate.
“It's therefore clear that plants first of all spread their roots in all directions, but the root obviously knows from the very first cell divisions on where it can find water and nutrients," says Daniel von Wangenheim, summarizing the results. “In this way, plants can react flexibly to an environment with fluctuating resources."
The result is based on many hours of film material recorded using Light Sheet Fluorescence Microscopy (LSFM), a technique developed by Ernst Stelzer. In a vivid video clip, Daniel von Wangenheim shows the root-branching process in slow motion. His tweet has already attracted considerable attention from his colleagues in the field. https://twitter.com/DvonWangenheim/status/1224365891292405760)
Publication: Daniel von Wangenheim, Jason Banda, Alexander Schmitz, Jens Boland, Anthony Bishopp, Alexis Maizel, Ernst H. K. Stelzer and Malcolm Bennett: Early developmental plasticity of lateral roots in response to asymmetric water availability, in Nature Plants (3 February 2020), https://doi.org/10.1038/s41477-019-0580-z)
A picture can be downloaded under: http://www.uni-frankfurt.de/85595433
Caption: Light Sheet Fluorescence Microscopy is based on two processes: 1) lateral illumination of the specimen with laser light along a plane and 2) detection of fluorescent light emitted from a thin volume centred around the illumination plane. The plant (Arabidopsis thaliana) is mounted in a three-dimensional assembly, stands upright in a plant-derived gel appropriate for the species and supplied with medium and light.
Image rights: Daniel von Wangenheim.
Further information: Dr Daniel von Wangenheim, Plant and Crop Sciences, School of Biosciences, University of Nottingham, UK, Email: firstname.lastname@example.org
Professor Ernst Stelzer, Institute for Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, Riedberg Campus, Tel.: +49(0)69-798-42547, Email: Ernst.Stelzer@physikalischebiologie.de
TruMotion: Goethe University signs agreement with universities in Lodz, Lyon, Milan and Thessaloniki / Application as "European University" envisaged
FRANKFURT. „TruMotion“ is the chosen name. Motion and exchange are at the heart of the alliance between the Goethe University and the universities in Lodz, Lyon, Milan and Thessaloniki, which was contractually sealed on Wednesday this week. The alliance is jointly planning a plethora of projects, programmes and courses of study.
At the faculty level, cooperation and exchanges have already been flourishing; now the managements of the five universities have joined forces in order to cooperate even more extensively in the future. On Wednesday the University of Lodz, the Université Lumière Lyon II, the Università Cattolica del Sacro Cuore in Milan, the University of Macedonia in Thessaloniki and the Goethe University signed the final cooperation agreements in the office of Prof. Birgitta Wolff, President of the University of Frankfurt. A first objective of the common endeavour is that the five universities intend to apply for the “European University" title and the associated funding from the European Union. However, irrespective of this, a wide range of ideas has already emerged in the run-up to yesterday's signing of the agreement.
"We want to become a brand", states Prof. Rolf van Dick, Vice President of the Goethe University responsible for International Affairs, on the sidelines of the meeting. The logo is already available: designed at the university in Lodz, Poland, it already adorns the joint documents. Five rays crossing a circle - abstract, yet allowing a breadth of associations. The now allied universities have many things in common and a lot of it has to do with the location: "All these cities are so-called Second Cities. This is to say that they are neither capitals nor the largest cities in their respective countries. However, they are multifaceted metropolises with a strong economy, good social cohesion and are steeped in a long civic and liberal tradition", elaborates van Dick. They share similar problems such as high rents and strong immigration. Still, the universities themselves also have a lot in common: they are all comprehensive universities with medicine but without engineering - with the exception of Thessaloniki.
Social cohesion, societal change and social identity – these are pressing topics when it comes to a joint long-term educational strategy and a common (virtual) "European campus". As a "European University", the collaboration could be substantiated and intensified.
In a highly acclaimed 2017 keynote speech, French President Emmanuel Macron proposed the establishment of twenty European universities by 2024, by which he did not mean newly created institutions, but rather the European networking and alignment of existing universities. At a challenging time for the European Union, university science should be strengthened as a pivotal driving force of European integration, so that the younger generation can develop a greater affinity with the European project. During a visit to the Goethe University in October of 2017, Macron emphatically reaffirmed his vision and therewith has also inspired the Goethe University to launch the initiative. After an initial attempt in the spring of 2019, it is now intended to resubmit the application to the “European University" programme. In this process, Goethe University is spearheading the consortium.
Focusing on strengths and jointly seeking solutions to challenges – is at the core of the cooperation. "In our regions, we have more start-ups collectively than Silicon Valley", says van Dick. The cities and counties of the university locations are on board as associate members of the alliance, in addition to the German-Italian Centre for the European Dialogue, the Villa Vigoni on Lake Como, and the Association of Science and Technological Transfer (ASTP), a non-profit organisation with the goal of conveying science to society.
The members of this week's meeting emerged with a sizeable workload. Key topics are mobility and exchange; a new joint degree programme in "Politics, economics and law" is to be established, which will entail elements of computer science as well as two stays abroad. Novel teaching formats are to be developed that do not always necessitate a change of location. Moreover, both scientific and administrative staff should also exchange ideas and familiarise themselves with the work methods and structures at other universities. In the long term, a joint technological infrastructure is also envisioned. These are grand goals that require perseverance – and money. Even if these endeavours do not come to fruition it is intended to continue and to hope for the support of their own countries and regions.
"Universities and their cities are to become 'Living Labs' and 'Agents of Change' that take place in the interest of the people", elucidates Rolf van Dick. "Mobility, internationalisation, joint research – these are our high hopes for this alliance", states Professor Dimitrios Kyrkilis, Vice President at the University of Macedonia in Thessaloniki. His Polish colleague from Lodz specifies for his location: "We would like to disseminate European ideas more strongly again in Eastern Europe and strengthen the position of science", says Professor Paweł Starosta.
An image is available for download by clicking: http://www.uni-frankfurt.de/85526960
Image text: The chairmanships of the universities in Lodz, Lyon, Milan and Thessaloniki have signed the cooperation agreements for "TruMotion" together with the University President Prof. Birgitta Wolff. Jointly they intend to apply for the "European University" title. From left: Prof. Birgitta Wolff, President of the Goethe University, Prof. Stelios D. Katranidis, Rector of the University of Thessaloniki, Prof. Antoni Różalski, Rector of the University of Lodz, Prof. Nathalie Dompnier, President of the University Lumière Lyon 2 und Edilio Mazzoleni, University of Milan. (Copyright: Uwe Dettmar)
New development makes tiny structural changes in biomolecules visible
FRANKFURT. Even more detailed insights into the cell will be possible in future with the help of a new development in which Goethe University was involved: Together with scientists from Israel, the research group led by Professor Harald Schwalbe has succeeded in accelerating a hundred thousand-fold the nuclear magnetic resonance (NMR) method for investigating RNA.
In the same way that a single piece of a puzzle fits into the whole, the molecule hypoxanthine binds to a ribonucleic acid (RNA) chain, which then changes its three-dimensional shape within a second and in so doing triggers new processes in the cell. Thanks to an improved method, researchers are now able to follow almost inconceivably tiny structural changes in cells as they progress – both in terms of time as well as space. The research group led by Professor Harald Schwalbe from the Center for Biomolecular Magnetic Resonance (BMRZ) at Goethe University has succeeded, together with researchers from Israel, in accelerating a hundred thousand-fold the nuclear magnetic resonance (NMR) method for investigating RNA.
“This allows us for the first time to follow the dynamics of structural changes in RNA at the same speed as they occur in the cell,” says Schwalbe, describing this scientific breakthrough, and stresses: “The team headed by Lucio Frydman from the Weizmann Institute in Israel made an important contribution here.”
The new types of NMR experiments use water molecules whose atoms can be followed in a magnetic field. Schwalbe and his team produce hyperpolarized water. To do so, they add a compound to the water which has permanently unpaired electron radicals. The electrons can be aligned in the magnetic field through excitation with a microwave at -271°C. This unnatural alignment produces a polarization which is transferred at +36°C to the polarization of the hydrogen atoms used in the NMR. Water molecules polarized in this way are heated in a few milliseconds and transfered, together with hypoxanthine, to the RNA chain. The new approach can in general be applied to observe fast chemical reactions and refolding changes in biomolecules at atomic level.
In particular the imino groups in RNA can be closely analyzed using this method. In this way, the researchers were able to measure structural changes in RNA very accurately. They followed a small piece of RNA from Bacillus subtilis, which changes its structure during hypoxanthine binding. This structural change is part of the regulation of the transcription process, in which RNA is being made from DNA. Such small changes at molecular level steer a large number of processes not only in bacteria but also in multicellular organisms and even humans.
This improved method will in future make it possible to follow RNA refolding in real time – even if it needs less than a second. This is possible under physiological conditions, that is, in a liquid environment and with a natural molecule concentration at temperatures around 36 °C. “The next step will now be not only to study single RNAs but hundreds of them, in order to identify the biologically important differences in their refolding rates,” says Boris Fürtig from Schwalbe’s research group.
Publication: Mihajlo Novakovic, Gregory L. Olsen, György Pintér, Daniel Hymon, Boris Fürtig, Harald Schwalbe, Lucio Frydman: A 300-fold enhancement of imino nucleic acid resonances by hyperpolarized water provides a new window for probing RNA refolding by 1D and 2D NMR, PNAS, 16 January 2020 https://doi.org/10.1073/pnas.1916956117
A picture can be downloaded from: http://www.uni-frankfurt.de/84996281
Caption: Frankfurt researchers followed the movements of this tiny molecule – just two-thousandths of the thickness of a piece of paper. The RNA aptamer changes its structure when it binds hypoxanthine. The green nucleobases change shape particularly quickly, the ones coloured blue more slowly. The grey regions do not change.
Further information: Professor Harald Schwalbe, Center for Biomolecular Magnetic Resonance (BMRZ), http://www.bmrz.de/, Institute of Organic Chemistry and Chemical Biology, Riedberg Campus, Tel.: +49(0)69-798-29737 or -40258, e-mail: email@example.com.