More than one million euro from EU collaborative project will flow to Frankfurt
FRANKFURT. Patients with rare diseases often go through a long history of suffering before finally receiving an accurate diagnosis. One reason for this is that the patient information necessary for research exists in varying languages and formats. This is set to change, thanks to a new European Joint Programme in which Goethe University plays an important role.
For patients with rare diseases, the trek from doctor to doctor, and expert to expert, with a long paper trail of physician’s letters, test results, and images is practically a given. And when a diagnosis is finally made, they are faced with the difficulty of obtaining the correct therapy. To help these patients more quickly, valuable information regarding the course of the disease and its therapy, which is currently kept at individual healthcare institutions, must be made available for essential Europe-wide research.
The European Joint Programme seeks to establish the technical and substantive requirements for clinical data to be used commonly for research purposes. Toward this end, Goethe University will receive the largest funding sum of all participating German institutions: more than one million euro over the coming five years.
In Frankfurt, the focus will be on developing tools to integrate and standardise patient data. This includes software solutions for setting up disease-specific patient registries in which specific patient data can be collected on an ongoing basis. This will result in a representative patient group whose data can be analysed much more simply thanks to its standardization.
“I think we can say with pride that in the future, Frankfurt will have a central role in Europe regarding the patient registry of rare diseases,” says Professor T.O.F. Wagner from the Frankfurt Reference Centre of Rare Diseases. Together with Dr. Holger Storf, Head of the Medical Informatics Group, he developed an open source registration platform for rare disease. The modules in it were used, among other things, to set up the European Rare Disease Registry Infrastructure. They also constitute the basis for the approved work in Frankfurt which, together with Professor Gernot Rohde, Head of Pneumonology at the University Hospital, should contribute to an improved interoperability of registries.
“Rare diseases are a great example of a field of research that greatly profits from coordination at the European and international level, and which therefore requires technical support,” says Dr. Holger Storf. The new project should help overcome fragmentation and make cooperation easier.
Within the EU project, already existing tools and programmes are to be consolidated and continued at a larger scale. Data from research, clinics, tests, processes, knowledge and know-how are to be shared throughout Europe in the future. In addition, an efficient model of financial support of all types of research on rare diseases – fundamental, clinical, health service – is to be introduced. The goal is an accelerated exploitation of research results in order to reduce the typical problems and ongoing suffering of patients.
Goethe University has already contributed to an improvement in the situation of patients with rare diseases through several different successful projects. In particular, the Mapping of Health Care Providers for People with Rare Diseases (www.se-atlas.de) deserves mention. It supports patients, their families, and health personnel in locating experts or patient organisations. The coordination and technical support of the European Reference Network for rare respiratory diseases (ERN-LUNG) is also in Frankfurt.
Professor T.O.F. Wagner, Frankfurt Reference Centre for Rare Diseases, Faculty of Medicine, Niederrad Campus, Tel.: +49 (69)- 6301 87899, email@example.com.
Dr. Holger Storf, Medical Informatics Group (MIG), University Hospital Frankfurt Frankfurt, Tel.: +49 (69) 6301-84438, firstname.lastname@example.org.
The biochemist Robert Tampé receives € 1.5 million for a Koselleck project with the German Research Foundation
FRANKFURT. Robert Tampé, Director of the Institute of Biochemistry at Goethe University, has received € 1.5 million from the German Research Foundation (DFG) for a Reinhart Koselleck project. Through this programme, the DFG enables outstanding researchers to pursue exceptionally innovative, higher-risk projects. Tampé will address the functioning of the immune system in and on the surface of cells.
“Our lives are repeatedly saved every day without us even knowing it,” states Robert Tampé. “Virtually undetected by us, our immune system constantly identifies and eliminates virus-infected cells, abnormal cells, and intra-cellular pathogens in an extremely efficient way. It’s a service provided by a well-functioning immune system.” Inversely, a malfunction or weakness in the immune system can lead to cancer, chronic illness and autoimmune diseases.
It is known that infected cells trigger an immune reaction by attracting the attention of T-cells. They present protein fragments (antigens) from their cellular proteins on the cell surface. More specifically, the antigens are transferred to the so-called major histocompatibility complexes (MHC-I) and presented to the T-cells. Editing and loading complexes associated with the MHC-I play a key role in controlling the immune response. Still, these complexes have only been investigated to a very limited extent so far.
“Viruses have developed sophisticated strategies to interfere with the antigen-loading of the MHC-I complexes and thus escape the attention of T-cells. In the Koselleck project, we want to elucidate some key mechanisms in the antigen processing,” says Tampé. The researcher expects that insights into the organization of these antigen quality control points will pave the way for a new understanding of intracellular multi-protein complexes associated with the cell membrane, and of chaperone complexes, which are important for the folding of proteins in the endoplasmic reticulum. In the long term, the findings should point to new therapy options for infections, autoimmune diseases, chronic illnesses and cancer.
Robert Tampé is the Director of the Institute of Biochemistry and the Collaborative Research Center “Transport and Communication through Biological Membranes”, in which scientists from the Max Planck Institute of Biophysics team up with researchers of Goethe University Frankfurt. He is one of the founders of the Cluster of Excellence “Macromolecular Complexes” funded by the German Excellence Initiative. Before coming to Frankfurt, he was Director of the Institute of Physiological Chemistry at the Faculty of Medicine of the University of Marburg, and Research Group Leader at the Max Planck Institute of Biochemistry in Martinsried and the Technical University Munich. He worked with Harden M. McConnell at Stanford University as Max Kade Fellow. He is an Honorary Professor of Kyoto University and was recently appointed Visiting Fellow at Merton College and the Department of Biochemistry at Oxford University.
As biochemist at the Biocenter in Frankfurt, Robert Tampé gained an international reputation for his fundamental contributions to the mechanistic understanding of antigen processing and to solving the question of how viruses avoid detection by the immune system. He also discovered the molecular machinery of ribosome recycling and provided structural and mechanistic insights into the quality control of protein biosynthesis. His main areas of interest include macromolecular complexes, membrane biology, as well as chemical and synthetic biology.
A picture may be downloaded at: www.uni-frankfurt.de/74506125
Credit: Goethe University/Uwe Dettmar
Developing brain networks act locally to build globally
One of the outstanding mysteries of the cerebral cortex is how individual neurons develop the proper synaptic connections to form large-scale, distributed networks. Now, an international team of scientists including researchers from Goethe University and the FIAS have gained novel insights from spontaneously generated patterns of activity by local networks in the early developing visual cortex. Apparently these form the basis for long-range neural connections that are established through brain activity over the course of cortical development.
Now, as published in Nature Neuroscience, scientists at the Max Planck Florida Institute for Neuroscience, Frankfurt Institute for Advanced Studies, Goethe University of Frankfurt, and the University of Minnesota have investigated the visual cortex of the ferret, an ideal model system to explore the early development of networks in the cortex. These are composed of thousands of neurons and are distributed over millimetres of the cortical surface. In the visual cortex, network activity encodes specific features of the visual scene like the orientation of edges and the direction of object motion.
By using calcium imaging techniques, the scientists were able to visualize with unprecedented resolution spontaneous activity patterns, i.e. patterns not produced by visual input. To their great surprise, the spontaneous activity patterns were highly correlated between distant populations of neurons – and in fact were so highly correlated that the activity of small populations of neurons could reliably predict coincident network activity patterns millimetres away, and these correlation patterns beautifully predicted the patterns of network activity evoked by visual stimulation.
In their next step, the researchers used this remarkable correspondence of spontaneous and visually-evoked network patterns to find out how the interaction of networks developed in the immature brain. By looking at the state of spontaneous activity patterns prior to eye opening, they expected to see a striking difference in the patterns of spontaneous activity because the long-range cortical connections that are thought to be the basis for distributed network activity patterns are absent in the immature cortex. To their surprise, they discovered robust long-range patterns of correlated spontaneous activity prior to eye opening, and found that they extended over distances comparable to what was seen in the mature brain.
Confronted with this paradox, the researchers first considered whether the correlated activity patterns could be spreading through chains of local cortical connections, similar to a forest fire. To test this intriguing possibility, Matthias Kaschube, Professor for Computer Science at Goethe University and Fellow at the Frankfurt Institute for Advanced Studies (FIAS), and his doctoral student Bettina Hein, built a computational model of the neural circuitry in the early visual cortex. They found that by using a set of parameters that are consistent with the organization of local cortical connections, the model could precisely reproduce the patterns of spontaneous long-range correlations they had observed experimentally, without the need for long-range connections.
Taken together, these results suggest that long-range order in the early developing cortex originates from neural activity driven by short-range connections. In other words, local connections build a network activity scaffold. Following the well-accepted plasticity rule ‘what fires together wires together’, activity mediated by local connections can then guide the subsequent formation of long-range network connections. In a twist of the oft-used phrase, ‘think globally, act locally’, developing cortical circuits act locally to achieve global effects. Future studies will test the prediction that activity dependent plasticity mechanisms shape the structure of long-range connections based on the instructive activity patterns derived from local cortical connections.
Gordon B Smith, Bettina Hein, Dave E Whitney, David Fitzpatrick, Matthias Kaschube: Distributed network interactions and their emergence in developing neocortex (2018) Nature Neuroscience. http://www.nature.com/articles/s41593-018-0247-5
An image can be downloaded here.
Caption: Spatial patterns of spontaneous correlation (example in figure on the left) in the immature visual cortex prior to eye-opening are distributed across several millimeters and resemble the layout of the response properties (example on the right) of visual cortex after eye-opening; Data: Max Planck Florida Institute.
Credit: Bettina Hein
Further information: Professor Matthias Kaschube, Institute for Computer Science and Frankfurt Institute for Applied Sciences, Riedberg Campus, Tel. +49 69 798-47521, email@example.com.
Researchers decode structure and function of docking domains in the biosynthesis of peptide natural products
FRANKFURT. Microorganisms often assemble natural products similar to industrial assembly lines. Certain enzymes, non-ribosomal peptide synthetases (NRPS) play a key role in this process. Biotechnologists at Goethe University have now been able to discover how these enzymes interact with each other. This brings them one step closer to their goal of engineering the production of such peptide natural products.
Many important natural products such as antibiotics, immunosuppressants, or cancer drugs are derived from microorganisms. These natural products are often small proteins or peptides which are generated in the cell by NRPS enzymes similar to a modern automobile factory: at each station additional parts are added to the basic structure until finally a completed automobile leaves the factory. With regard to the 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 including unusual amino acids.
If larger peptides are generated by these systems, often several NRPS enzymes – or assembly lines – operate successively. The order in which this happens is determined by docking domains. These are small regions at the end of the assembly lines that fit with the next NRPS enzyme in line like a key in a lock. Although the basic principles of these NRPS interactions have been known for a long time, the structure of the docking domains was unknown until now. The research groups led by Professor Jens Wöhnert form the Institute of Molecular Biosciences and Professor Helge Bode from Molecular Biotechnology at Goethe University have now been able to successfully explain this.
“We were able to determine the structures of individual docking domains and, for the first time, an NRPS docking domain pair as well,” explains Carolin Hacker, who is a PhD student in Jens Wöhnert’s group. “This made it possible to clarify the rules for the interaction of the docking domains and to change them in such a way that new natural products will be generated,” adds Xiaofeng Cai, postdoctoral researcher in Helge Bode’s group.
“We are only at the beginning of our research: We need structures of additional and structurally diverse docking domains so that in the end we can utilise them like building blocks. Our goal is to connect various biosynthesis pathways and create totally new substances” Wöhnert explains. “Nature has been quite inventive in this area, and there are apparently numerous different ways to mediate the interaction of these complexes,” adds Bode.
Research in this area continues in both groups as part of the LOEWE research cluster MegaSyn. The first results on the structures of additional docking domains are quite promising.
Publication: Carolin Hacker, Xiaofeng Cai, Carsten Kegler, Lei Zhao, A. Katharina Weickhmann, Jan Philip Wurm, Helge B. Bode, Jens Wöhnert: Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS, Nature Communications, https://www.nature.com/ncomms/, DOI: 10.1038/s41467-018-06712-1
You can download an image at: www.uni-frankfurt.de/74390329
Caption: 3D structure of an NRPS docking domain pair. The docking domains of NRPS B (green) connects to the fitting docking domain of NRPS C (magenta) via a β-leaflet.
Further information: Professor Jens Wöhnert, Institute for Molecular Biosciences, Faculty 15, Riedberg Campus, Tel. +49 69 798-29785, firstname.lastname@example.org
Professor Helge B. Bode, Molecular Biotechnology, Faculty 15, Riedberg Campus, Tel.: +49 69 798-29557, email@example.com
Barry Eichengreen appointed Visiting Professor for Financial History 2019
FRANKFURT. Barry Eichengreen, University of California, Berkeley, will hold the Visiting Professorship of Financial History at Goethe University Frankfurt’s House of Finance next year. The professorship is endowed by Metzler Bank and Friedrich Flick Förderungsstiftung.
Barry Eichengreen is George C. Pardee and Helen N. Pardee Professor of Economics and Political Science at the University of California, Berkeley. His research focuses on the history and current operation of the international monetary and financial system.
His most recent books include The Populist Temptation: Economic Grievance and Political Reaction in the Modern Era (2018), How Global Currencies Work: Past, Present, and Future with Livia Chitu and Arnaud Mehl (2017), Hall of Mirrors: The Great Depression, the Great Recession, and the Uses – and Misuses – of History (2015), and Exorbitant Privilege: The Rise and Fall of the Dollar and the Future of the International Monetary System (2011) (shortlisted for the Financial Times and Goldman Sachs Business Book of the Year Award in 2011). One of the best known books by Barry Eichengreen is Golden Fetters: The Gold Standard and the Great Depression, 1919–1939 (1992) which argues that a main cause for the world depression of the 1930ies was the structurally flawed and poorly managed international gold standard. In his most widely cited paper (with Tamim Bayoumi in 1993) he argued that the European Union was less suitable as a Single Currency Area than the United States.
Professor Eichengreen was educated at Yale University in New Haven, CT (M.A in Economics, M.Phil. in Economics, M.A. in History and a Ph.D. in Economics) and the University of California, Santa Cruz (B.A. in Economics and Political Science). He is a Research Associate at NBER (National Bureau of Economic Research) and a Research Fellow at CEPR (Centre for Economic Policy Research). He received a doctor honoris causa from the American University in Paris and, in 2010, the Schumpeter Prize from the International Schumpeter Society. Eichengreen has been named one of Foreign Policy Magazine's 100 Leading Global Thinkers, and he is a past president of the Economic History Association (2010-11 academic year).
During his stay in Frankfurt in May 2019, Barry Eichengreen will head a workshop for young scholars on the occasion of the 50th anniversary of the IBF (Institut für Bank- und Finanzgeschichte) on “Financial History – Reflections on the Past to Tackle Today’s Key Finance Questions” and deliver the keynote address in an international research conference at Goethe University. He will also give a seminar titled “Topics in Macroeconomic History” in the Ph.D. program of the University’s Graduate School GSEFM at the House of Finance.
Professor Eichengreen is the fifth holder of the Goethe University Visiting Professorship of Financial History. In the context of this professorship, distinguished international experts in banking and financial history are invited to share their research insights and methods with researchers, students and the interested public in Frankfurt. Cooperation partners are the Research Center SAFE at the House of Finance and the Institut für Bank- und Finanzgeschichte. Previous Visiting Professors were Benjamin Friedman, Harvard University (2015), Caroline Fohlin, Emory University, Atlanta (2016), Hans-Joachim Voth, University of Zurich (2017) and Harold James, Princeton University (2018). The Visiting Professorship was initially endowed by Metzler Bank and Edmond de Rothschild Group in 2014 on the occasion of Goethe University’s centennial. Since 2018 it is sponsored by Metzler Bank and Friedrich Flick Förderungsstiftung.
Picture material may be downloaded at: http://www.muk.uni-frankfurt.de/74041865?
Further Information: Dr. Stephanie Collet, Research Center SAFE, House of Finance, Campus Westend, Tel. +49 69 798-30041, firstname.lastname@example.org