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
University honours the founder of the "Notgemeinschaft" with a column
FRANKFURT. He was long forgotten: Philipp Schwartz, who saved many scientists who lost their jobs during the national socialism era. Persecuted himself, he narrowly escaped arrest on 23 March 1933 and immediately fled to Zurich. Here the Frankfurt pathology professor founded the "Notgemeinschaft Deutscher Wissenschaftler im Ausland". The university placed a column in front of the main university hospital building in memory of the valiant efforts of the displaced neuropathologist. During the opening of the dedication ceremonies, the Dean of the Faculty of Human Medicine, Prof. Pfeilschifter, called Philipp Schwartz a "shining light in the darkest epoch of German history".
Two contemporary witnesses also took part in the dedication ceremonies: Dr. Susan Ferenz-Schwartz and Kurt Heilbronn. Philipp Schwartz's daughter was moved that "my father received his place at the university and in the history of Frankfurt University after so many years, after almost two generations." Kurt Heilbronn in turn is the son of Prof. Alfred Heilbronn, who the "Notgemeinschaft" sent to the Istanbul University in 1935, where he established the Institute of Pharmacobotanics.
As the consul general of the Republic of Turkey, Ufuk Ekici, emphasised in his welcoming speech, it is a little known fact that between 1933 and 1945 Turkey offered a safe haven to about 300 dismissed German scientists, artists, architects and politicians who worked here for brief or longer periods. The consul general thanked them for their important contributions to shaping modern Turkey. It was Philipp Schwartz who made it all happen. In the summer of 1933, he travelled to Istanbul. In initial negotiations with Turkish government representatives, he already attained the hiring of 30 professors at the University Istanbul which had just opened in 1933; a full seven of them from Frankfurt am Main – a one of a kind group placement of scientist emigrates during the Nazi period.
A card file was established in Zurich under Schwartz's direction. This was the basis for the list with names and information on 1794 dismissed scientists who were registered with the "Notgemeinschaft" in 1937. A bound copy stood in a shelf at the Frankfurt Institute for Neuroscience since the 1980s – until the sociologist and medical historian Dr. Gerald Kreft from the Edinger-Institute at Goethe-Universität started investigating. All of this was completely unknown in Zurich, where Schwartz had founded the "Notgemeinschaft" in the city mansion of his father-in-law Professor Sinai Tschulok. Thus the results of Kreft's research were met with open ears there. In April 2014, the city dedicated a grave of honour to Philipp Schwartz.
The "Notgemeinschaft" was the first contact point for dismissed German professors looking for work abroad. "Its unique knowledge base made it the information centre for all corresponding international aid organisations", Gerald Kreft tells us.
In the late summer of 1933, Schwartz handed management of the "Notgemeinschaft" to the privy council Dr. Fritz Demuth, the persecuted curator of the Berlin School of Commerce. He moved the head office to London at the end of 1935. In 1936 it published the "List of Displaced German Scholars" financed by the Rockefeller Foundation, in order to find new employment opportunities abroad for 1794 scientists. Up until 1945 the "Notgemeinschaft" was involved as an intermediary for over 2600 dismissed persons from Germany, Austria and Bohemia.
In his welcome speech, the director of the Frankfurt Institute of Pathology, Prof. Martin-Leo Hansmann, gave a reminder of the ground-breaking studies on the topic of cerebral birth trauma which Schwartz performed here in the 1920s. After leading the Institute of Pathology in Istanbul for twenty years, in the 1950s Schwartz attempted to return to his former domain in Frankfurt am Main. While he was formally reinstated as professor at the University of Frankfurt in 1957 in the course of the Federal Republic's "Wiedergutmachung", the Faculty of Medicine denied his return as professor "for age reasons alone". Schwartz moved to the USA, where he lead his own research institute at the Warren State Hospital in Pennsylvania, until 1976 as an internationally renowned neuropathologist.
During the dedication ceremony for the Schwartz column, Professor Schubert-Zsilavecz in the position of Vice President of the Goethe-Universität apologised to Schwartz for its behaviour during and after the National Socialism period.
Information: Dr. Gerald Kreft, Edinger Institute, Deutschordenstraße 46, Phone.: (069) 6301-84166, G.Kreft@gmx.net.
German Research Foundation grants new Collaborative Research Centre to the Goethe University – seven million Euros for historians, ethnologists, philosophers and historians of law
FRANKFURT. Humanities scholars in Frankfurt can begin a mammoth project on 1 January 2015: Between 2015 and 2018, historians, ethnologists, philosophers and law historians will be able to draw on more than 6 million Euros in an attempt to shed light on a global historical issue that stretches from ancient times to the present day. The German Research Foundation (DFG) yesterday granted a Collaborative Research Centre (CRC), currently the only one of its kind in the Humanities faculty of the Goethe University. It is entitled: "Discourses on weaknesses and resource regimes". Over the next three years, some 50 scientists will collaborate in this research association, among them about 40 junior researchers.
What is the purpose of this CRC? Here is an example: Contemporary historian Prof. Dr. Christoph Cornelißen intends to examine the debate involving the political, economic and cultural decline of Europe, which raged throughout the entire 20th century. A number of players – politicians, business representatives, publishers and scientists – feared for Europe's position in the world; Advancing Americanisation and the Yellow Peril are just two key phrases. Europe, they believed, was no longer a match for the growing pressure in world markets, and was also losing ground in international education rankings. The discourses on weaknesses were regularly interspersed with calls to mobilise all existing resources, from people and raw materials to organisations and ideas. The idea was to set up a new political, economic and societal order to prevent Europe's decline, galvanising ideas of a unified Europe. This is just a rough outline of the thesis; the work will now involve taking a closer look at the players and establishing with greater precision how resources can be developed from weaknesses.
"Discourses on weaknesses crop up everywhere. Examples that are often discussed include the Late Roman Empire and China in the 19th century. Yet rather different ones also come to mind, such as situations where weak areas of knowledge initially prevailed, as demonstrated by the budding material sciences of the early 20th century", explained the spokesperson of the new Collaborative Research Centre, Prof. Dr. Hartmut Leppin. "We anticipate a high potential of insight from being able to compare such seemingly disparate topics at an appropriate level of abstraction." When diagnosing the deficits, the scientists will always keep an eye on the self-perception of the players and how they are perceived from a distance.
The fact that weaknesses can develop into strengths is often demonstrated when the discourse on weaknesses mobilises the search for resources. It is this interplay that captures the scientists' interest. The humanities scholars in Frankfurt are fully aware that resources do not equate to raw materials: "Rather, we are interested in what it means to perceive a shortage of raw materials, which then develops into a discourse on weaknesses while the search goes on for other resources", Leppin says. This involves very diverse resources, depending on the sub-project: science, kinship, sanctity, nationalism, information, economic calculations, to name a few. "The wide range of resources can only be dealt with from contrasting disciplinary and temporal perspectives. Our aim is to compare cultures and epochs, in order to be able to provide highly generalised findings", the CRC spokesman explained. Ethnologists and law historians are grouped around a heavily historical nucleus, here in cooperation with the Max-Planck-Institute for European Legal History.
The cooperating scientists also intend to establish an approximation between European history and the history of East and South East Asia as well as Latin America. By way of example, ethnologist Prof. Dr. Susanne Schröter, like Leppin a principal investigator at the Frankfurt cluster of excellence "The Formation of Normative Order", intends to address the question of why it is almost impossible to assert Western models of organisation, such as a monopoly on the legitimate use of physical force, in many post-colonial countries. The particular focus here will fall on Indonesia and the Philippines. For instance, which resources do indigenous groups generate that elude state control? Are acephalous peoples with their egalitarian societies, which are oriented towards achieving political and social equality for their members, perhaps the ones who are truly strong, despite their political weaknesses? Is their conduct more reasonable than that of societies produced by state regulation or which have willingly integrated into such? These are the questions ethnologists seek answers to on the ground.
The participants at the Collaborative Research Centre wish to contribute a humanist perspective to our society's self-reflection. "The question of how to treat resources, their shortage and protection, is discussed in what are at times very heated and politically influential discourses on weaknesses. We have known this since the famous Club of Rome report of 1972, if not before", explains Leppin. "I believe the shortage of resources is one of the key challenges facing us today. However, we must avoid focussing on material resources to the exclusion of all else." Other acting CRC spokespeople besides Susanne Schröter are sinologist Prof. Dr. Iwo Amelung and science historian Prof. Dr. Moritz Epple.
The President of Goethe University, Prof. Dr. Werner Müller-Esterl, views the grant to the Collaborative Research Centre, the ninth at Goethe University, as further evidence of the influence of Frankfurt humanities scholars, and its historians in particular. "The grant is another highlight in a very successful year; back in March, the historians were awarded the DFG research group on "Personnel Decisions in Key Sociopolitical Positions". I would like to take this opportunity to congratulate Hartmut Leppin and his group on this successful application. It further underscores the profile of the Goethe University in the humanities."
Other projects of the historians and contributing humanities scholars are highly popular among sponsors.
The Volkswagen Foundation deemed the Research Centre for Historical Humanities at Goethe University to be "original, innovative and exemplary", and in July 2014 provided it with a grant of 826,000 Euros.
In total the German Research Foundation (DFG) will be establishing eight Collaborative Research Centres (CRC), the authorising committee decreed in Bonn at its Autumn meeting yesterday. The Frankfurt Collaborative Research Centre is the only one of the eight to involve the humanities. The new CRCs are being sponsored with a total of 62 million Euros. There is an additional 20 per cent programme allowance for indirect costs arising out of research projects. Two of the eight centres are CRC/Transregios (TRR), which are distributed across several research locations.
Prof. Dr. Hartmut Leppin, Faculty of History, Department of Ancient History, Campus Westend, Tel. (069) 798 32462, email@example.com
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Professor of Ancient History Dr. Hartmut Leppin is the spokesperson of the new Collaborative Research Centre "Discourse on weaknesses and resource regimes"
The new "L-CSC" supercomputer at the GSI Helmholtz Centre for Heavy Ion Research is ranked as the world's most energy-efficient supercomputer
FRANKFURT/NEW ORLEANS. The new "L-CSC" supercomputer at the GSI Helmholtz Centre for Heavy Ion Research is ranked as the world's most energy-efficient supercomputer. The new supercomputer reached first place on the "Green500" list published in New Orleans on Thursday, comparing the energy efficiency of the fastest supercomputers around the world. With a computing power of 5.27 gigaflops per watt, the "L-CSC" has also set a new world record for energy efficiency among supercomputers. Second and third place on the new list are held by two Japanese supercomputers (Suiren, Tsukuba and Tsubame-KFC, Tokyo).
"L-CSC" was developed at the Frankfurt Institute for Advanced Studies (FIAS) and the Goethe University Frankfurt. The supercomputer was financed by the GSI Helmholtz Centre for Heavy Ion Research in Darmstadt, where it is used for simulations and calculations in basic physics research. It is also slated to prepare experiments at the large international accelerator centre FAIR (Facility for Antiproton and Ion Research), which is currently under development in Darmstadt. The super-fast and energy-saving supercomputer was developed by the Frankfurt computer sciences professor Volker Lindenstruth and his team. It primarily uses efficient cooling and conventional graphics cards, in order to reduce the energy consumption and investment cost for the supercomputer.
Obtaining the world champion title for the "L-CSC" is already the third success for the FIAS scientists within four years on the worldwide who's-who list of green supercomputers: in 2010, the Frankfurt supercomputer "LOEWE-CSC" at Goethe University reached eighth place as Europe's most environmentally-friendly supercomputer. Two years later, the Saudi Arabian computer "SANAM", developed in Frankfurt and Darmstadt, reached second place on the "Green500" list. The world record crowns this series. The list is based on an assessment of how many floating point operations per second a supercomputer optimized for speed achieves with one watt of power.
"L-CSC" is still under construction. At the moment, 56 out of a total of 160 servers are installed. This already makes the computer in Darmstadt one of the world's fastest. On the worldwide "Top500" ranking – which is based purely on speed – it currently holds 168th place with 316.7 trillion floating point operations per second – about three thousand times faster than a normal office PC. And it will perform calculations about three times faster once it is completed in the coming weeks.
"L-CSC" was developed on the basis of the "LOEWE-CSC" and "SANAM" supercomputers, and relies even more heavily on graphics cards for its computing power. Its name is based on its predecessor. However, "L-CSC" performs computations considerably more quickly than its four-year-old predecessor "LOEWE-CSC" and achieves over seven times the computing power with the same amount of energy. This was achieved by using more optimized high speed graphics chips and improved software developed at the FIAS.
The investment costs for "L-CSC" are around two million Euros. When it comes to supercomputers, saving energy isn't just a question of protecting the environment, but is also important in saving on the electricity bill. Thus "L-CSC" runs with significantly lower operating costs than less energy-efficient supercomputers which are just as fast.
The person who developed the "L-CSC", Chairman of the Board at FIAS, IT Director at GSI and professor for high-performance computing architecture at the Goethe-Universität Frankfurt, Volker Lindenstruth, feels that the top ranking of his supercomputer confirms the long-standing energy efficiency efforts: "We are also making a contribution which will allow supercomputers to be used increasingly in industry, because society also requires more and more computing power, whether for technical developments, big data applications, cloud computing or other things."
From a technical point of view, "L-CSC" is a computing cluster, a network of connected computers. Upon completion, the computer is slated to consist of a total of 160 servers (ASUS ESC4000 G2S/FDR), with 1,600 processor cores, each of which contains two Intel-Ivy-Bridge processors and four AMD FirePro graphics cards. Every server has 256 Gigabytes of working memory. The servers are connected through an FDR Infiniband network. In theory, "L-CSC" is capable of providing a peak computing power of 1.7 petaflops with double precision, so 1.7 quadrillion
floating point operations per second in this configuration. This makes it the fourth-fastest supercomputer in Germany.
Information: FIAS Public Relations Office, Reiner Korbmann, c/o Science&Media, firstname.lastname@example.org; Phone ++49(0)89-642 17 50; Frankfurt Institute for Advanced Studies (FIAS), Ruth-Moufang-Str. 1, 60438 Frankfurt am Main, Phone ++49(0)69-798 44100; email@example.com.
Hypoxia protein also regulates growth factors
FRANKFURT/GIESSEN. Healthy cells reduce their growth when there is a lack of oxygen (hypoxia). This makes it even more surprising that hypoxia is a characteristic feature of malignant tumours. In two publications in the current edition of the "Nature Communications" journal, researchers from Goethe University and the Justus-Liebig-University of Giessen report on how cancer cells succeed at circumventing the genetic program of growth inhibition.
It has long been known that PHD proteins (prolyl-hydroxylase domain proteins) play a key role among the regulators of hypoxia. They control the stability of the hypoxia-induced transcription factors (HIFs) which govern the adaptation of cells to a lack of oxygen. The two teams led by Professor Amparo Acker-Palmer, Goethe University, and Professor Till Acker, Justus-Liebig-University, have now discovered that a special PHD protein, PHD3, also controls the epidermal growth factor receptor (EGFR).
In healthy cells, PHD3 responds to stressors such as a lack of oxygen by stimulating the uptake of EGF receptors into the cell interior. Growth signals are down-regulated by this internalisation. "We have discovered that PHD3 serves as a scaffolding protein, binding to central adapter proteins such as Eps15 and Epsin1 in order to promote the uptake of EGFR into the cells," says Acker-Palmer. This process is disrupted in tumour cells due to the loss of PHD3. As a result, the internalisation of EGFR is suppressed, which leads to overactivity of EGFR signals, and thus to uncontrolled cell growth.
The research team was able to show that the loss of PHD3 is a crucial step in the growth of human malignant brain tumours (glioblastomas). The tumour cells thus become refractory to the growth-inhibiting signals under hypoxia. "Clinically, this discovery is highly relevant, because it shows an alternative mechanism for the hyperactivation of the EGF receptor that is independent of its genetic amplification. It can be therapeutically suppressed by EGFR inhibitors," explains Till Acker, a neuropathologist at the University of Giessen.
"Our work shows an unexpected and new function of PHD3 on the interface of two currently red-hot research areas: Oxygen measurement and EGFR signalling," Acker-Palmer explains. "This once again proves how significant growth receptor internalisation is to the development of cancer." This connection was already shown by the research team in 2010 for tumour angiogenesis (Sawamiphak et al, Nature 2010).
Henze et al: Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR; Nature communications 25.11.2014; DOI 10.1038/ncomm6582
Garvalov et al.: PHD3 regulates EGFR internalization and signalling in tumours, Nature communications 25.11.2014, DOI: 10.1038/ncomms6577
Information: Prof. Amparo Acker-Palmer, Institute for Cell Biology and Neuroscience and the Buchmann Institute for Molecular Life Sciences, Campus Riedberg,Phone ++49(0)69 798- 42563, Acker-Palmer@bio.uni-frankfurt.de.Prof. Till Acker, Institute of Neuropathology, University Clinic Giessen and Marburg GmbH, Arndtstraße 16, 35392 Gießen, Phone ++49(0)641 99-41181, firstname.lastname@example.org