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Biochemists uncover an elementary energy metabolism process: They unlocked the structure of mitochondrial complex 1, a large protein complex in the respiratory chain , and at the same time learnt new aspects of its function.
Mitochondria produce ATP, the energy currency of the body. The driver for this process is an electrochemical membrane potential, which is created by a series of proton pumps. These complex, macromolecular machines are collectively known as the respiratory chain. The structure of the largest protein complex in the respiratory chain, that of mitochondrial complex I, has been elucidated by scientists from the Frankfurt "Macromolecular Complexes" cluster of excellence, working together with the University of Freiburg, by X-ray diffraction analysis.
"Mitochondrial complex I plays a critical role in the production of cellular energy and has also been associated with the onset of diseases, such as Parkinson's disease", explains Volker Zickermann, an assistant professor at the Institute for Biochemistry II at the Goethe University. In order for the respiratory chain to function, there must be consistently sufficient amounts of oxygen available in all the cells in our bodies. The energy released during biological oxidation is used to transport protons from one side of the inner mitochondrial membrane to the other. The resulting proton gradient is the actual "battery" for ATP synthesis.
What surprised the researchers: Previous studies suggested that redox reactions and proton transport in complex I occurred spatially isolated from one another. The Frankfurt scientists in Zickermann's working group and the working groups led by Prof. Harald Schwalbe and Prof. Ulrich Brandt have now been able to deduce how the two processes are connected to one another from the detailed analysis of the structure. They have therefore made an important contribution towards the understanding of an elementary process in energy metabolism.
It has long been known that complex I can switch reversibly between an active and inactive form. This has been interpreted as a protective mechanism against the formation of dangerous free oxygen radicals. The structure now clearly indicates how these two forms are differentiated from one another and transformed into one another. "The research results thus also give important information about the molecular basis of a pathophysiologically significant property of complex I that may be significant for the extent of tissue damage after a myocardial infarction," explains Zickermann.
Mechanistic insight from the crystal structure of mitochondrial complex I
V Zickermann et al.; Science, doi: 10.1126/science.1259859; 2015
The ABC4Trust project will present its results in the offices of the Hessian State Delegation to the European Union in Brussels
FRANKFURT/BRUSSELS One of the most widely recognized EU projects of Frankfurt's Goethe University will present its results on Tuesday (20/1) in the offices of the Hessian State Delegation to the European Union in Brussels: "ABC4Trust" is the acronym for an international project, for which Frankfurt Professor Kai Rannenberg is the spokesman. The project has developed solutions that will markedly increase the trustworthiness of personal data in the Internet while offering optimal privacy protection. In addition to the President of Goethe University, Prof. Dr. Birgitta Wolff, participants in the demonstration of the project results this coming Tuesday will also include Günther Oettinger or a representative of the Commissioner for Digital Economy and Society and Jan Albrecht, member of the European Parliament, Greens/EFA and rapporteur for the European General Data Protection Regulation.
The first three letters of ABC4Trust stand for "attribute-based credentials". The intention is to supply any Internet provider with only the relevant features (attributes) of the user in each case, but the attributes will also be furnished with a type of credibility certificate (credential) from an entity trusted by the provider. Here is an example: If someone buys a book over the Internet, the online merchant does not need to know anything about the purchaser's date of birth, blood group or hobbies shared with friends. Such information may be important in other Internet contexts, for example when contacting a health insurer or in a chat with friends. But what is of prime importance to the online merchant is that the user's account data is correct. The user can demonstrate this with a bankcard or credit card.
The user can store his "credentials" in a type of wallet, from which he can display the important attributes in each case. This is clearly better for the user than the current situation in the Internet, in which identity information is repeatedly queried from the source, the so-called "identity provider". Rannenberg, who has occupied the Deutsche Telekom Chair for "Mobile Business & Multilateral Security" since 2002, comments: "Since 2009, ABC4Trust has been developing a Privacy ABC-based system for electronic identification that allows users to shield their privacy and simultaneously offers security to their counterpart – the service provider. We have successfully tested the system in two pilot applications; a communications platform in a school in Sweden and an anonymous course evaluation system at the University of Patras."
A total of approximately 50 scientists have cooperated in various sub-projects, and the EU has supported ABC4Trust with just under 9 million Euros since 2010 from the 7th Research Framework Programme. In addition to Goethe University, the international project consortium includes Unabhängiges Landeszentrum für Datenschutz Schleswig-Holstein, Darmstadt Technical University and non-university research institutions from Denmark and Sweden, corporations such as IBM, Microsoft and Nokia Networks, and an encryption specialist from France.
A variety of pilot applications will be presented at the closing event in Brussels. The project also looks at ways in which the two advanced technologies for identity management using "attribute-based credentials" (both from American providers: U-Prove from Microsoft and Idemix from IBM) can be sensibly linked. The ABC4Trust project has been built using both of these technologies, so that the user is not dependent on one management system or the other, but can instead choose between them. ABC4Trust is also intended to be an openly accessible technology, which is a research condition required by the EU. The project team therefore had to bring together all the players. "That was not always particularly easy, but we managed to do it!", notes programme director Prof. Rannenberg.
At the presentation this coming Tuesday, he and his international colleagues will also offer a look forward at future developments in identity management. These include the use of these privacy ABCs in mobile devices such as smartphones and tablets, so that privacy can be better protected in those fields as well. The guests at this event in the Hessian State Delegation Office will also include: Michael Garcia (Deputy Director of the "National Strategy for Trusted Identities in Cyberspace" of the National Institute for Standardization and Technology (NIST) of the US Department of Commerce) and Achim Klabunde (Manager of the IT policy sector for the European Data Protection Supervisor).
Participation in the final event (20 January 9:30 am – 6:00 pm) is still open for interested parties and journalists; registration at: https://abc4trust.eu/index.php/events/177-summit-announce
Information Prof. Dr. Kai Rannenberg, Deutsche Telekom Endowed Professor of "Mobile Business & Multilateral Security", Department of Economics and Business Administration, Campus Westend, Tel. 069-79834701, Kai.Rannenberg@m-chair.de, firstname.lastname@example.org; https://www.datenschutzzentrum.de/projekte/abc4trust/, English-language project website at https://abc4trust.eu/summit
The Frankfurt ancient historian is distinguished with the top prize of the German Research Foundation
FRANKFURT. The steering committee of the German Research Foundation last week in Bonn announced that the Frankfurt ancient historian Prof. Hartmut Leppin was awarded the 2015 Gottfried Wilhelm Leibniz Prize, which is endowed with a grant of 2.5 million Euro. Prof. Werner Müller-Esterl, President of Frankfurt University, congratulated the researcher who was selected along with seven other scholars. Müller-Esterl called the prize a "distinction for a scholar who has made significant contributions to profiling the historical studies at Goethe University through his research on ancient history. The prize is the 'icing on the cake' of the anniversary year at Goethe University." Leppin has become renowned internationally thanks to his diverse publications and his involvement in joint research projects with good international exposure. "Leppin is the fifth recipient of the Leibniz Prize at Goethe University since 2010 alone, underscoring the level of excellence in research at our university", Müller-Esterl is happy to say. "And it is already the fourth award to be won by the humanities and social sciences."
The 51-year-old historian has been with Goethe University as a professor of ancient history since 2001, declining reputable appointments in Hannover, Cologne and the Humboldt University in Berlin in its favour. His research centres around the history of political thought in Ancient Greece and the history of Christianity in antiquity. Many of his publications extend across the boundaries between antiquity and the Middle Ages. His research covers a period of 600 years – from the birth of Christ to the beginnings of Islam.
Leppin is extremely well connected in the humanities and social sciences, and also seeks dialogue with fellow historians. This is evidenced by his latest success in obtaining a grant from the DFG for the special research centre "Discourses on weaknesses and resource regimes", for which Leppin acts as speaker. Additionally, the ancient historian is involved in the Frankfurt Cluster of Excellence "The Formation of Normative Orders", as well as participating in the research training group on "theology as a science". Furthermore, he is a supporter of the Research Centre for Historical Humanities at Goethe University. The Volkswagen Foundation describes this centre as "original, innovative and exemplary" and is providing 820,000 Euro for the centre's work.
Leppin's monograph "Das Erbe der Antike" (The Legacy of Antiquity), published by C.H. Beck Verlag 2011, also highly appreciated by non-historians and drew a lot of attention. He clearly demonstrates that Europe as we know it today originated in the Mediterranean world of antiquity, and illustrates the history of antiquity based on three ideas: freedom, empire and true faith. He addresses important eras with these terms: "freedom" for Ancient Greece during the Attic democracy, "empire" for the Roman Empire, and finally the empire of late antiquity with "true faith".
Leppin is currently focusing most of his efforts in his research on "Christianisations in the Roman Empire". This work is being sponsored by the German Research Foundation with a 500,000 Euro grant over five years within the framework of a Koselleck project. While lots of work has been done on Hellenisation and Romanisation, little research has been done on Christianisation to date. The project is intended to close this gap through theoretical and empirical research into fundamental processes during the Imperial and Late Antiquity periods, which are important to the broader history within and beyond Europe. Christianisation occurred at varying times and degrees in different regions and fields, such as royal self-portrayal and the use of Christian symbols in art. This is why Leppin intentionally uses the term Christianisations in the title. Leppin's book "Antike Mythologie in christlichen Kontexten der Spätantike" (Ancient Mythology in the Christian Contexts of Late Antiquity) is due for publication by de Gruyter soon. This comprehensive project ties in well with Leppin's research in the excellence cluster "The Formation of Normative Orders". There he is researching imperial politics and religious spheres in the 3rd century. With the endowment from the Leibniz Prize, Leppin is planning to delve more deeply into the question of the degree to which the Christian Empire permitted or restricted religious and cultural diversity. The ancient historian is hoping to make inroads into research on early Islam and to help answer the question of the historical significance of the spread of three monotheistic religions.
Biography of the Leibniz Prize recipient: Leppin studied history, Latin, Greek and pedagogy at Marburg, Heidelberg, Pavia, and Rome. He completed his first state examination for teaching History and Latin in 1988, received his doctorate from Marburg in 1990 with a study on Roman stage artists, followed by a post-doc at the Free University of Berlin in 1995 with a study on the Greek church historians of the 5th century AD. He has been teaching at Goethe University since 2001. He is liaison professor of the German National Academic Foundation and sits on the DFG review board. Leppin is also active as advisor and associate editor for various publications: Antike Welt, Centro Ricerche e Documentazione sull’antichità classica, Handwörterbuch der antiken Sklaverei, Historische Zeitschrift, Millennium, and Reallexikon für Antike und Christentum.
Hartmut Leppin is the 16th scientist at Goethe University to be awarded this prize. In 1986, the philosopher Jürgen Habermas and the later Nobel Prize winner and biochemist Hartmut Michel received the coveted prize. They were followed by historian Lothar Gall (1988), physicist Reinhard Stock (1989), legal historian Michael Stolleis (1991), mathematician Claus-Peter Schnorr (1993), physicist Theo Geisel (1994), chemist Christian Griesinger (1998), paleontologist Volker Mosbrugger (1999), biologist Stefanie Dimmeler (2005), historian Bernhard Jussen (2007), economist Roman Inderst (2010), philosopher Rainer Forst (2012) biochemist Ivan Dikic (2013) and legal scholar Armin von Bogdandy (2014).
The Frankfurt COLTRIMS Reaction Microscope provides new Results - Current Publication in the Prestigious Journal Nature Communications"
FRANKFURT Frankfurt physicists have once again contributed to resolving a disputed matter of theoretical physics. Science has long since known that, contrary to the old school of thought, helium forms molecules of two, three or even more atoms. Exactly what helium consisting of three atoms looks like, however, has been disputed by theoretical physicists for about 20 years. Besides the intuitive assumption that the three identical components form an equilateral triangle, there was also the hypothesis that the three atoms are arranged linearly, in other words in a row. As the group of scientists led by Prof. Dr. Reinhard Dörner and his graduate student Jörg Voigtsberger report in the current edition of the prestigious journal Nature Communications, using the COLTRIMS reaction microscope, they were able to demonstrate that the truth lies in between the two.
"Nature gets out of it quite elegantly here: We looked at the helium molecule” under our reaction microscope, and it was found that He3 is like a cloud," says Voigtsberger, whose dissertation is the source of the publication results. "It makes no difference whether it's linear or triangular or another configuration: all are equally probable, as is typical for quantum mechanics." Moreover, Voigtsberger and his coworkers' results put an end to an idea carried over from school days: The He3 molecule does not consist of a solid structure, as is the case, for example, with the hydrogen molecule H2 and the carbon dioxide molecule CO2, in which the individual atoms quasi impinge directly on one another. In contrast, He3 is like a cloud – the distance between the atoms is roughly ten times the atomic radius.
Finally, Voigtsberger and Dörner report that one variant of the He3 molecule behaves in an unusual way: normal helium atoms consist of two protons and two neutrons. If one of the three helium atoms is replaced by the lighter isotope, which consists only of two protons and one neutron, then the molecule will be in a so-called quantum halo state: the lighter isotope is further away from the other two atoms than should be possible according to classic physics. "One can visualise this as ping pong balls in a soup bowl," explains Dörner. "Normal atoms collect at the bottom of the bowl, at a minimum of the potential. If they overcome the potential mountain, in other words the wall of the bowl, they will be completely separated from the molecule. Thus the lighter helium isotope is, as it were, outside of the bowl but, due to the quantum mechanical tunnel effect, it still "notices" the atoms in the bowl and cannot simply fly away."
The COLTRIMS reaction microscope, with which the experiments on helium molecules were conducted, has already demonstrated its versatility many times: in 2013, Dörner's work group had already been able to resolve a dispute of theoretical physics. In that case, the COLTRIMS experiments proved that the position of the Danish physicist Niels Bohr in the "Einstein-Bohr debates" 80 years ago was correct and, shortly before that, other physicists from the atomic physics work group used COLTRIMS to "film" the destruction of a molecule by a strong laser pulse – a reaction so fast that it cannot be captured by an ordinary camera.
Publication: J. Voigtsberger et al., Imaging the structure of the trimer systems 4He3 and 3He4He2 in: Nature Communications, 5:5765, DOI: 10.1038/ncomms6765
Information: Prof. Dr. Reinhard Doerner, Institut für Kernphysik [Institute of Nuclear Physics], Campus Riedberg, Telephone (069) 798-47003, email@example.com
A research team from Kiel University (CAU) and Goethe University Frankfurt has jointly created a synthetic surface on which the adhesion of E. coli bacteria can be controlled
A research team from Kiel University (CAU) and Goethe University Frankfurt has jointly created a synthetic surface on which the adhesion of E. coli bacteria can be controlled. The layer, which is only approximately four nanometres thick, imitates the saccharide coating (glycocalyx) of cells onto which the bacteria adhere such as during an infection. This docking process can be switched on and off using light. This means that the scientists have now made an important step towards understanding the relationship between sugar (carbohydrates) and bacterial infections. Their research results embellish the front page of the latest issue of the renowned journal Angewandte Chemie (Applied Chemistry).
The bond between either cells and other cells or cells and surfaces is vital to organisms, for example in the development of internal organs and tissue. However, these mechanisms are also involved in illness and infections. The E. coli bacteria used in the experiment can cause urinary tract infections, meningitis, sepsis and other severe illnesses. In order to understand and treat these illnesses, researchers need to decipher the molecular processes which allow the bacteria cells to dock onto the healthy host cells.
This often happens by way of proteins, which interact with carbohydrate structures on the surface of the host cell by means of a complex fit principle (simplified: lock-and-key principle). The Kiel/Frankfurt study demonstrates for the first time that the spatial orientation of the carbohydrate structures is crucial to this process. However, in natural glycocalyx, a mere nanometre thick polysaccharide layer covering all cells, the relationships are still too complex to uncover how proteins and carbohydrates identify each other.
In Collaborative Research Center (SFB) 677 'Function by Switching', Professor Thisbe K. Lindhorst, chemist at Kiel University, and her team construct molecules which, when irradiated by light at different wavelengths, operate as biological switches. Together with the working group around the surfaces specialist Professor Andreas Terfort (Frankfurt University), the Lindhorst group has now produced a system with which the orientation of the saccharide docking points, and thus the bonding of E. coli bacteria, can be controlled. To do this, the scientists covered an extremely thin gold surface with a precisely defined saccharide covering, coupled to azobenzene. This is a hydrocarbon containing a nitrogen bridge and operating as a hinge controlled by light. The bonding properties of the saccharide coating can now be switched using this method: if the researchers irradiate their system with light with a wavelength of 365 nanometres, considerably fewer pathogenic bacteria cells can adhere to the synthetic surface. The saccharide molecules turn away from the bacteria, in a sense, and can no longer be recognised. When switched on by 450 nanometre wavelength light waves, on the other hand, the structures reorientate such that the bacteria cells can dock on once again. In this way, E. coli adhesion can be controlled.
'By employing a layer system on a solid surface, in combination with a photo-hinge, the complex dynamics of a real glycocalyx can be reduced to the principal processes and thus be better understood', explains Terfort. 'It should be possible to transfer this novel approach to other biological boundary layer systems.'
'Based on our model system, glycocalyx recognition and bonding effects can be precisely defined and investigated from a completely new angle', says Lindhorst. 'If we can learn how to influence glycocalyx in the context of the relationship between health and healing, it will lead to a revolution in medicinal chemistry.'
Switching of bacterial adhesion to a glycosylated surface by reversible reorientation of the carbohydrate ligand. Theresa Weber, Vijayanand Chandrasekaran, Insa Stamer, Mikkel B. Thygesen, Andreas Terfort and Thisbe K. Lindhorst. Angew. Chem. 48/2014 DOI: 10.1002/ange.201409808 and 10.1002/anie.201409808 (Angew. Chem. Int. Ed.)
Photos and figures are available for download:
Caption: Left: E. coli bacteria can dock onto the saccharide molecules of the synthetic glcocalyx using the FimH protein. Right: When irradiated with light at a wavelength of 365 nanometres, the saccharide molecules on the surface bend away and cannot be recognised by the proteins. The bacteria can then no longer dock onto the host cell.
Figure/Copyright: Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.
Caption: Controlled bonding: the adhesion of bacteria onto saccharide molecules on the glycocalyx model can be reversibly controlled by light.
Figure/Copyright: Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.
Caption: Scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip.
Caption: Thisbe K. Lindhorst (photo) and her team control the adhesion of E. coli bacteria using switchable saccharide molecules.
Photo/Copyright: Stefan Kolbe
Caption: Surfaces specialist Andreas Terfort (photo) from Goethe University Frankfurt
Photo/Copyright: Larissa Zherlitsyna
Prof. Dr Thisbe K. Lindhorst
Christian-Albrechts-Universität zu Kiel
Otto Diels-Institut für Organische Chemie
Tel.: +49 (0)431 880-2023
Prof. Dr Andreas Terfort
Tel.: +49 (0)69798-29180