Researchers from Goethe University discover a new clinical biomarker to improve treatment of leukaemia
Because it is impossible to predict which acute myeloid leukaemia (AML) patients will benefit, all patients are routinely treated with chemotherapy although only some will respond to the treatment. Researchers from Goethe-University Frankfurt have now discovered a novel biomarker that enables the detection of therapy responders and non-responders with high accuracy. In addition, their research reveals new hope for patients who currently cannot be effectively treated.
The anti-cancer drug cytarabine provides the basis of chemotherapies directed against AML. Cytarabine needs to be activated in cancer cells by the addition of phosphate groups to exert its anti-cancer effects. Prof Jindrich Cinatl (Institut für Medizinische Virologie, Goethe-Universität, Acting Director: Prof Volkhard Kempf) investigated with his research group (funded by the Frankfurter Stiftung fürkrebskranke Kinder) cytarabine-resistant AML cells from the Resistant Cancer Cell Line (RCCL) collection (www.kent.ac.uk/stms/cmp/RCCL/RCCLabout.html) that he runs together with Prof Martin Michaelis (University of Kent, Canterbury, UK). ProfCinatl discovered that the toxicity of cytarabine against AML cells correlates with the expression of the cellular enzyme SAMHD1, which enables to predict the sensitivity of AML cells to cytarabine.
Following this initial finding, a consortium led by Prof Cinatl together with Prof Oliver Keppler (who moved from the Institut für Medizinische Virologie, Goethe-Universität to Ludwig-Maximilians-Universität, München during the project) showed that SAMHD1 removes the phosphate residues from the active form of cytarabine and thereby reverses it into its inactive state. In a cooperation with clinicians (led by Prof Hubert Serve, Medizinische Klinik II, Goethe-Universität) it was shown that SAMHD1 levels determined in leukaemia cells also enabled the prediction of the response of AML patients to cytarabine-based chemotherapies with high accuracy. This introduces SAMHD1 as clinical biomarker that can guide cytarabine-based chemotherapies only to such patients that are very likely to respond and spares patients who are unlikely to respond from toxic side effects. In addition, the Frankfurt-led team showed that inhibition of SAMHD1 effectively sensitises cytarabine-resistant AML cells to cytarabine-based chemotherapies, opening future prospects for the treatment of patients for whom currently no effective therapy exists.
The research was published in the journal Nature Medicine on 19th December 2016 and can be found here:
Federal State of Hessen paves the way for shared professorship with Fritz Bauer Institute
FRANKFURT/WIESBADEN. Boris Rhein, Hessen’s Minister for Science and the Arts, announced on the 16th of December that historian Professor Dr. Sybille Steinbacher had been called to the first chair for Holocaust Studies in Germany. In their decision to appoint her, senate and president’s office of Goethe University Frankfurt followed the recommendation of a committee of international experts. The creation of a chair for research into the history and impact of the Holocaust was anchored in a financial agreement signed with Goethe University Frankfurt and the Fritz Bauer Institute back in July 2015, after which the formal procedure for filling the new position was launched. The Foundation Board of the Fritz Bauer Institute has confirmed its approval of Steinbacher’s appointment. The Federal State of Hessen is co-funding the professorship with an additional € 150,000 per year.
Boris Rhein, Minister for Science: “We are very happy that this important professorship can now be filled by a particularly renowned expert. This is a milestone on the route to a better understanding of Nazi crimes and the history of their impact up to the present day. This joint appointment by Goethe University Frankfurt and the Fritz Bauer Institute will also further enhance the integration of university and institute-based research.”
The historian, who currently still heads the Institute of Contemporary History at the University of Vienna, will take up her post on the 1st of May 2017. Steinbacher is a proven expert in the field of Holocaust Studies and has conducted extensive research on the subject. The professorship, which will be based at the Faculty of Philosophy and History of Goethe University Frankfurt, is shared with the Fritz Bauer Institute and sponsored by the Federal State of Hessen.
Professor Birgitta Wolff, President of the University: “Goethe University Frankfurt is particularly committed, not least due to its own chequered history, to the intellectual reappraisal of the Holocaust. Sybille Steinbacher will dedicate herself to this subject with our full support and fit in well as a colleague too.”
The new chair will also be in charge of the Fritz Bauer Institute, which the federal state government will continue to sponsor to the tune of about € 375,000 in 2017. That means a total sum of well over € 500,000 from federal state funds for the professorship and the institute in future.
“Linking the new professorship with the directorship of the Fritz Bauer Institute is a unique opportunity which we are using to advance the scientific reappraisal of the Holocaust to the greatest degree possible. The Fritz Bauer Institute is a centre of research and education of highest international acclaim and its importance radiates beyond the borders of Hessen too. Above all the confrontation with the ethical and moral structures with which the Holocaust is justified even up to the present day makes the research work so valuable and unique”, explained Boris Rhein, Minister for Science.
Jutta Ebeling, Chairwoman of the Foundation Board of the Fritz Bauer Institute: “With Sybille Steinbacher, the University and the Institute have appointed an internationally acknowledged scholar who combines the scientific investigation of Nazi crimes with tremendous sensitivity towards the subject’s significance in present times. We look forward to welcoming Sybille Steinbacher to Frankfurt am Main in the near future.”
Sybille Steinbacher already handled the subject of mass extermination in Nazi Germany in her Masters thesis at LMU Munich, which was also published in book form: “Dachau: The Town and the Concentration Camp in the Third Reich”. She then expanded her new approach in her doctoral dissertation, which she wrote at Ruhr-Universität Bochum and was entitled “‘Model Town’ Auschwitz. Germanisation Policy and Murder of Jews in East Upper Silesia”. This later formed the basis for an internationally much acclaimed standard reference work on the subject, which was translated into numerous languages. A second field in which Steinbacher is working is the social history of the early Federal Republic. Her monograph “How sex came to Germany. The struggle for morality and decency in the early Federal Republic” was based on her professorial thesis submitted at Friedrich Schiller University Jena in 2010.
Sybille Steinbacher has spent much of her career abroad: She was a scholar at the German Historical Institute Warsaw and Harvard University as well as a fellow at the United States Holocaust Memorial Museum. She was already visiting professor at Goethe University Frankfurt for the history and impact of the Holocaust in 2010 in conjunction with the Fritz Bauer Institute. Sybille Steinbacher has been professor of Contemporary History/Comparative Dictatorship, Violence and Genocide Studies at the University of Vienna since 2010 and Corresponding Member of the Austrian Academy of Sciences since 2014.
Universal behaviour detected in Mott metal-insulator transition
FRANKFURT. Whether water freezes to ice, iron is demagnetized or a material becomes superconducting – for physicists there is always a phase transition behind it. They endeavour to understand these different phenomena by searching for universal properties. Researchers at Goethe University Frankfurt and Technische Universität Dresden have now made a pioneering discovery during their study of a phase transition from an electrical conductor to an insulator (Mott metal-insulator transition).
According to Sir Nevill Francis Mott’s prediction in 1937, the mutual repulsion of charged electrons, which are responsible for carrying electrical current, can cause a metal-insulator transition. Yet, contrary to common textbook opinion, according to which the phase transition is determined solely by the electrons, it is the interaction of the electrons with the atomic lattice of the solid which is the determinant factor. The researchers have reported this in the latest issue of the “Science Advances” journal.
The research group, led by Professor Michael Lang of the Physics Institute at Goethe University Frankfurt, succeeded in making the discovery with the help of a homemade apparatus which is unique worldwide. It allows the measurement of length changes at low temperatures under variable external pressure with extremely high resolution. In this way, it was possible to prove experimentally for the first time that it is not just the electrons which play a significant role in the phase transition but also the atomic lattice - the solid’s scaffold.
“These experimental results will herald in a paradigm shift in our understanding of one of the key phenomena of current condensed matter research”, says Professor Lang. The Mott metal-insulator transition is namely linked to unusual phenomena, such as high-temperature superconductivity in copper oxide-based materials. These offer tremendous potential for future technical applications.
The theoretical analysis of the experimental findings is based on the fundamental notion that the many particles in a system close to a phase transition not only interact with their immediate neighbours but also “communicate” over long distances with all other particles. As a consequence, only overarching aspects are important, such as the system’s symmetry. The identification of such universal properties is thus the key to understanding phase transitions.
“These new insights open up a whole new perspective on the Mott metal-insulator transition and permit more sophisticated theoretical modelling of the phase transition”, explains Dr. Markus Garst, Senior Lecturer at the Institute of Theoretical Physics of Technische Universität Dresden.
The research work was funded by the German Research Foundation in the framework of the Collaborative Research Centre/Transregio “Condensed Matter Systems with Variable Many-Body Interactions” led by Professor Michael Lang.
Elena Gati, Markus Garst, Rudra S. Manna, Ulrich Tutsch, Bernd Wolf, Lorenz Bartosch, Harald Schubert, Takahiko Sasaki, John A. Schlueter, and Michael Lang, Breakdown of Hooke’s law of elasticity at the Mott critical endpoint in an organic conductor, Science Advances 2, e1601646 (2016).
A picture can be downloaded from: www.uni-frankfurt.de/64342454
Caption: Electrons embedded in the atomic lattice – the components of a solid. The mutual repulsion of the electrons prevents them from coming into close contact. This impedes the electron flow and the system can become an insulator (originator: Dr. Ulrich Tutsch)
Further information: Professor Dr. Michael Lang, Physics Institute, Riedberg Campus, Tel.: +49(0)69-798-47241, Michael.Lang@physik.uni-frankfurt.de.
New class of peptide from bacteria is a potential insecticide
FRANKFURT. Nature often produces a whole weaponry of active ingredients to ensure it is well prepared for any scenario that might occur. Pharmacists and medical experts have meanwhile learnt from this, since pathogens develop resistance more easily to single active drugs than to a combination therapy. The research group led by Professor Helge Bode has now discovered a whole class of new peptides with which bacteria are able to kill insect larvae.
The peptides, known as rhabdopeptide/xenortide peptides (RXPs), are produced exclusively by the bacterial genera Photorhabdus and Xenorhabdus. They live in symbiosis with nematodes, together with which they infect and kill insect larvae. Since many RXPs are toxic for eukaryotic cells (including insect cells) and are produced by many different strains of Xenorhabdus and Photorhabdus, they presumably play a very important role during infection.
One single strain of bacteria can produce up to 40 RXP derivates. As the research group, which is led by Professor Helge B. Bode, Merck Endowed Professor of Molecular Biotechnology at Goethe University Frankfurt, reported in the latest issue of Nature Chemistry, it was surprising to see that only a maximum of four enzymes is required for their production. Bode compares them with classic chemical catalysts for the formation of polymer chains. His group has successfully solved the mechanisms responsible for the production of the unusually high diversity of RXPs.
Why do the bacteria produce a whole library of RXPs instead of single compounds? The researchers explain that the bacteria cannot control into which insect larvae they are delivered by their nematode host. However, in order to survive they must be able to kill any insect quickly and efficiently and direct the mixture of substances at perhaps completely different target sites in the insect cells at the same time. “Imagine shooting with a shotgun”, explains Bode, “even if you’re a poor marksman, there’s a good chance that the spray of bullets will ensure that at least one hits the target!”
Future work will focus on detecting the exact mode of action of the RXPs and identifying, by means of structure-activity analysis, particularly potent derivates, which can then be produced biotechnologically or chemically and perhaps used as insecticides.
Xiaofeng Cai, Sarah Nowak, Frank Wesche, Iris Bischoff, Marcel Kaiser, Robert Fürst and Helge. B. Bode: Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design, in: Nature Chemistry, DOI: 10.1038/NCHEM.2671
A picture can be downloaded from: http://www.uni-frankfurt.de/64290802
Further information: Prof. Dr. Helge Bode, Merck Endowed Professor of Molecular Biotechnology, Tel.: +49(0)69-798-29557, H.Bode@bio.uni-frankfurt.de.
Atomic physicists in Frankfurt measure bond length/precise testing of quantum-mechanical tunnel effect
FRANKFURT. Helium atoms are loners. Only if they are cooled down to an extremely low temperature do they form a very weakly bound molecule. In so doing, they can keep a tremendous distance from each other thanks to the quantum-mechanical tunnel effect. As atomic physicists in Frankfurt have now been able to confirm, over 75 percent of the time they are so far apart that their bond can be explained only by the quantum-mechanical tunnel effect.
The binding energy in the helium molecule amounts to only about a billionth of the binding energy in everyday molecules such as oxygen or nitrogen. In addition, the molecule is so huge that small viruses or soot particles could fly between the atoms. This is due, physicists explain, to the quantum-mechanical “tunnel effect”. They use a potential well to illustrate the bond in a conventional molecule. The atoms cannot move further away from each other than the “walls” of this well. However, in quantum mechanics the atoms can tunnel into the walls. “It’s as if two people each dig a tunnel on their own side with no exit”, explains Professor Reinhard Dörner of the Institute of Nuclear Physics at Goethe University Frankfurt.
Dörner’s research group has produced this helium molecule in the laboratory and studied it with the help of the COLTRIMS reaction microscope developed at the University. The researchers were able to determine the strength of the bond with a level of precision not previously achieved and measured the distance between the two atoms in the molecule. “The helium molecule is something of a touchstone for quantum-mechanical theories, as the value of the binding energy theoretically predicted is heavily dependent on how accurately all physical and quantum-mechanical effects were taken into account”, explains Dörner.
Even the theory of relativity, which is otherwise mainly required for astronomical calculations, had to be incorporated here. “If even just a small mistake occurs, the calculations produce major deviations or even indicate that a helium molecule cannot exist at all”, says Dörner. The precision measurements performed by his research group will serve as a benchmark for future experiments.
Two years spent taking measurements in the cellar
Dörner’s research group began investigating the helium molecule back in 2009, when the German Research Foundation awarded him a Reinhart Koselleck Project and funding to the tune of € 1.25 million. “This type of funding is risk capital, as it were, with which the German Research Foundation supports experiments with a long lead time”, explains Dörner. He was thus able to design and set up the first experiments with his group. Initial results were achieved by Dr. Jörg Voigtsberger in the framework of his doctoral dissertation. “In the search for atoms which ‘live in the tunnel’, Jörg Voigtsberger spent two years of his life in the cellar”, recalls Dr. Till Jahnke, senior lecturer and Voigtberger’s supervisor at the time. It is there, in the cellar, that the laser laboratory of the atomic physics group is housed.
Stefan Zeller, the next doctoral researcher, considerably improved the equipment with the help of Dr. Maksim Kunitski and increased measurement precision still further. To do so, one of his tasks was to shoot at the very weakly bonded helium molecule with FLASH, the free-electron laser at the DESY research centre in Hamburg and the largest "photon canon" in Germany. “Stefan Zeller’s work was remarkable. It was his untiring effort, his excellent experimental research skills and his ability not to be disheartened by temporary setbacks which made our success possible at all”, remarks Professor Dörner, Zeller’s doctoral supervisor.
Already beforehand the results have attracted considerable interest at national and international level. They will now appear in the renowned journal “Proceedings of the National Academy of Sciences of the United States of America (PNAS)” and are also part of the research work for which the group was awarded the Helmholtz Prize 2016.
S. Zeller, M. Kunitski, J. Voigtsberger, A. Kalinin, A. Schottelius, C. Schober, M. Waitz, H. Sann, A. Hartung, T. Bauer, M. Pitzer, F. Trinter, C. Goihl, C. Janke, M. Richter, G. Kastirke, M. Weller, A. Czasch, M. Kitzler, M. Braune, R. E. Grisenti, W. Schöllkopf, L. Ph. H. Schmidt, M. Schöffler, J. B. Williams, T. Jahnke, and R. Dörner:
Imaging the He2 quantum halo state using a free electron laser, in: PNAS, DOI
A caricature can be downloaded from: www.uni-frankfurt.de/64324412
“When two loners are forced to share a bed, they move well beyond its edges to get away from each other.”
Further information: Professor Dr. Reinhard Dörner, Institute of Nuclear Physics, Max-von-Laue-Str. 1, Tel.: +49(0)-798-47003, email@example.com;
PD Dr. Till Jahnke, Institute of Nuclear Physics, Max-von-Laue-Str. 1, Tel.: +49(0)-798-47025, firstname.lastname@example.org