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Repeated stimulation enlarges dendritic spines
FRANKFURT. Even in adult brains, new neurons are generated throughout a lifetime. In a publication in the scientific journal PNAS, a research group led by Goethe University describes plastic changes of adult-born neurons in the hippocampus, a critical region for learning: frequent nerve signals enlarge the spines on neuronal dendrites, which in turn enables contact with the existing neural network.
Practise makes perfect, and constant repetition promotes the ability to remember. Researchers have been aware for some time that repeated electrical stimulation strengthens neuron connections (synapses) in the brain. It is similar to the way a frequently used trail gradually widens into a path. Conversely, if rarely used, synapses can also be removed – for example, when the vocabulary of a foreign language is forgotten after leaving school because it is no longer practised. Researchers designate the ability to change interconnections permanently and as needed as the plasticity of the brain.
Plasticity is especially important in the hippocampus, a primary region associated with long-term memory, in which new neurons are formed throughout life. The research groups led by Dr Stephan Schwarzacher (Goethe University), Professor Peter Jedlicka (Goethe University and Justus Liebig University in Gießen) and Dr Hermann Cuntz (FIAS, Frankfurt) therefore studied the long-term plasticity of synapses in new-born hippocampal granule cells. Synaptic interconnections between neurons are predominantly anchored on small thorny protrusions on the dendrites called spines. The dendrites of most neurons are covered with these spines, similar to the thorns on a rose stem.
In their recently published work, the scientists were able to demonstrate for the first time that synaptic plasticity in new-born neurons is connected to long-term structural changes in the dendritic spines: repeated electrical stimulation strengthens the synapses by enlarging their spines. A particularly surprising observation was that the overall size and number of spines did not change: when the stimulation strengthened a group of synapses, and their dendritic spines enlarged, a different group of synapses that were not being stimulated simultaneously became weaker and their dendritic spines shrank.
“This observation was only technically possible because our students Tassilo Jungenitz and Marcel Beining succeeded for the first time in examining plastic changes in stimulated and non-stimulated dendritic spines within individual new-born cells using 2-photon microscopy and viral labelling,” says Stephan Schwarzacher from the Institute for Anatomy at the University Hospital Frankfurt. Peter Jedlicka adds: “The enlargement of stimulated synapses and the shrinking of non-stimulated synapses was at equilibrium. Our computer models predict that this is important for maintaining neuron activity and ensuring their survival.”
The scientists now want to study the impenetrable, spiny forest of new-born neuron dendrites in detail. They hope to better understand how the equilibrated changes in dendritic spines and their synapses contribute the efficient storing of information and consequently to learning processes in the hippocampus.
Publication: Structural homo- and heterosynaptic plasticity in mature and adult new-born rat hippocampal granule cells. DOI: 10.1073/pnas.1801889115 (Jungenitz et al. PNAS, 115:E4670 2018)
Picture material can be downloaded at: www.uni-frankfurt.de/72306770
Caption: The dendrites of newborn neurons (green) are covered with spines, similar to the thorns on a rose stem (Credit: Tassilo Jungenitz).
Further information: Dr Stephan Schwarzacher, Institute for Anatomy I, Faculty of Medicine, Niederrad Campus, Tel.: +49 (0)69 6301-6914, firstname.lastname@example.org
Hannah Petersen investigates the state of matter shortly after the Big Bang
FRANKFURT. The theoretical physicist Hannah Petersen has been awarded the Zimanyi Medal of the Hungarian Academy of Sciences. The award is in honor of her work on relativistic heavy ion collisions. This young researcher has been the leader of a Helmholtz Young Investigators Group at GSI Helmholtzzentrum für Schwerionenforschung since 2012 and is a professor teaching at the Goethe University in Frankfurt. Her studies are important for the work on the future accelerator center FAIR, which is currently being constructed at GSI.
Prof. Petersen received the award at the Quark Matter Conference in Venice, where she also presented the latest results from her working group. The quark matter conference is the largest conference in this field with over 800 participants. Hannah Petersen is the youngest member of the International Advisory committee of the Quark Matter Conference.
She is working on new theoretical descriptions of the state of matter shortly after the Big Bang. Relativistic heavy ion collisions offer a way to study strongly interacting matter under the extreme conditions that prevailed at that time. “By accelerating lead or gold nuclei to almost the speed of light and smashing them together, we can reach temperatures and densities that existed in the early universe only microseconds after the Big Bang,” she says to describe her research. At such high energy densities, the basic theory of strong interaction, the quantum chromodynamics, predicts the existence of a new phase of matter—the quark-gluon plasma—which expands explosively at extremely high pressure.
Prof. Petersen was one of the first to recognize and investigate how the course of this explosion was affected by density and temperature variations resulting from quantum effects. By comparing theoretical and experimental data she was able to propose a frequently cited hybrid model that illustrates the dynamics and viscosity of the plasma as a function of the respective initial state of the quantum fluctuation.
The future accelerator center FAIR will provide the researchers with conditions that otherwise only exist in outer space. The work of Prof. Petersen and her Young Investigators Group is an important element for drawing essential conclusions from the experiments. Her main goal is to develop a transport approach for the dynamical description of heavy ion reactions at FAIR using state-of-the-art scientific computing. The scientific managing director of GSI and FAIR, Prof. Paolo Giubellino, is delighted about the young physicist’s award. “Hannah Petersen’s analytical method lays an important new foundation for experimental measurements at FAIR. Her work has now been rightly honored with the highest award for young theoretical physicists in the area of heavy ion physics,” he said.
The Zimanyi Medal is awarded by the Wigner Research Center for Physics of the Hungarian Academy of Sciences in Budapest. The prize was created in memory of the nuclear physicist József Zimányi, who died in 2006. Zimányi was also a member of the Hungarian Academy of Sciences and a professor at the Institute for Particle and Nuclear Physics (RMKI). The medal is awarded to theoretical physicists under the age of 40 years who have achieved important international recognition and impact in the area of theoretical high-energy physics.
Picture material can be downloaded at: www.uni-frankfurt.de/72219632
Caption: Hannah Petersen and Tamás Sándor Bíró from the Zimanyi Foundation at the award ceremony in Venice. Photo: Rosario Turrisi
Further information: Professor Hannah Petersen, Institute for Theoretical Physics, Faculty of Physics, Riedberg Campus, Tel.: +49(0)69-798- 4752, email@example.com.
Scientists develop simulation code for new generation of supercomputers
FRANKFURT. Even after the direct measurement of their gravitational waves, there are still mysteries surrounding black holes. What happens when two black holes merge, or when stars collide with a black hole? This has now been simulated by researchers from Goethe University Frankfurt and the Frankfurt Institute for Advanced Studies (FIAS) using a novel numerical method. The simulation code "ExaHyPE" is designed in such a way that it will be able to calculate gravitational waves on the future generation of “exascale” supercomputers.
The challenge in simulating black holes lies in the necessity of solving the complex Einstein system of equations. This can only be done numerically and exploiting the power oi parallel supercomputers. How accurately and how quickly a solution can be approximated depends on the algorithm used. In this case, the team headed by Professor Luciano Rezzolla from the Institute of Theoretical Physics at the Goethe University and the FIAS achieved a milestone. Over the long term, this theoretical work could expand the experimental possibilities for detecting gravitational waves from other astronomical bodies besides black holes.
The novel numerical method, which employs the ideas of the Russian physicist Galerkin, allows the computation of gravitational waves on supercomputers with very high accuracy and speed. “Reaching this result, which has been the goal of many groups worldwide for many years, was not easy,” says Prof. Rezzolla. “Although what we accomplished is only a small step toward modelling realistic black holes, we expect our approach to become the paradigm of all future calculations.”
Exascale Computers – as fast as the human brain?
Rezzollas team is part of a Europe-wide collaboration with the objective of developing a numerical simulation code for gravitational waves, "ExaHyPE", that can exploit the power of “exascale” supercomputers. While they have not yet been built, scientists around the world are already studying how to make use of exascale machines. These supercomputers represent the future evolution of today's "petascale" supercomputers, and are expected to be able to perform as many arithmetic operations per second as there are insects on Earth. This is a number with 18 zeros and it is assumed that such supercomputers will be comparable to the capacity of the human brain.
While they are waiting for the first “exascale” computers to be built, the ExaHyPE scientists are already testing their software at the largest supercomputing centres available in Germany. The biggest ones are those at the Leibniz supercomputing centre LRZ in Munich, and the high-performance computing centre HLRS in Stuttgart. These computers are already constructed with more than 100,000 processors and will become much larger soon.
Simulating tsunamis and earthquakes
Because of the analogies in the underlying equations, the new mathematical algorithms allow the investigation of tsunamis and earthquakes in addition to astrophysical compact objects such as black holes and neutron stars. Developing the new computer algorithms, which will be able to mathematically describe solids, liquids and gases within the theories of electromagnetism and gravitation, is the goal of the research project funded by the European Commission through the European Union's Horizon 2020 Research and Innovation Programme. The Frankfurt-based scientists work closely together with colleagues from Munich (Germany), Trento (Italy) and Durham (Great Britain).
“The most exciting aspect of the ExaHyPE project is the unique combination of theoretical physics, applied mathematics and computer science,” says Professor Michael Dumbser, leader of the Applied Mathematics team in Trento. “Only the combination of these three different disciplines allows us to exploit the potential of supercomputers for understanding the complexity of the universe.“
Publication: Michael Dumbser, Federico Guercilena, Sven Köppel, Luciano Rezzolla, und Olindo Zanotti: Conformal and covariant Z4 formulation of the Einstein equations: Strongly hyperbolic first-order reduction and solution with discontinuous Galerkin schemes. Phys. Rev. D 97, 084053 – Published 30 April 2018. https://journals.aps.org/prd/abstract/10.1103/PhysRevD.97.084053
Further information: Prof. Dr. Luciano Rezzolla, Frankfurt Institute for Theoretical Physics, Faculty of Physics and Frankfurt Institute for Advanced Studies, Riedberg Campus, Tel. +49 (0) 69 798-47871, firstname.lastname@example.org.
ExaHyPE Projekt: http://exahype.eu/
Looking for bachelor graduates with strong interest in research
FRANKFURT. The successful master scholarship “Goethe Goes Global“ is expanding its scope this year: whereas previously applications were only possible for 20 programs, now almost 80 programs are eligible – in other words, all consecutive master programs at the Goethe university. The target group remains students who received their first degree with distinction from a university abroad, and have a strong research interest. "This means Goethe University has expanded the range of subjects that can be selected by master candidates interested in research," Professor Manfred Schubert-Zsilavecz, Vice President for "Third Mission" at Goethe University, is happy to report. "In this way, we hope to further boost the internationalisation process at Goethe University."
The application deadlines correspond to the deadlines for the master programs. This year, the deadline is 31st May for many study programmes with admissions restrictions and 31st August for most study programmes with no admissions restrictions. German citizens who received their degree abroad may also apply. Good German language skills are not always required, as many study programmes are conducted in English only. The amount of the scholarships is higher than DAAD's: 1,000 Euro per month for the two years normally required to complete the degree.
Professor Rolf van Dick, Vice President for Internationalisation, Young Academics, Diversity and Equality explains the distinctive features of "Goethe Goes Global": "Some programmes offer the opportunity of integrating the scholarship awardees in the University's research groups early on. These include cross-discipline natural and life sciences, as well as human and social sciences. The internationalisation of research, study and teaching therefore all go hand in hand at Goethe University."
The programme, which was set up in 2016, is financed by Goethe University's Johanna Quandt Anniversary Foundation. The deceased honorary senator set up the fund in 2014 on the occasion of Goethe University's 100th anniversary. The programme will initially run until at least 2019. A continuation is desired, and depends, among other things, on how many master scholarship awardees go on to get their doctorate, preferably at the Goethe University.
The 24 awardees who made their way to Frankfurt from four different continents have already proved excellent ambassadors for the programme, promoting the scholarship directly among fellow students in their native countries. Their experiences can be viewed in a short video: https://video-182.uni-frankfurt.de/Mediasite/Play/8963c25f72354fb8ac003bf8b79032ee1d
They equally emphasize the advantages of university education, the integrated practical training, and the city, and also talk about the regular group get-togethers organised for them by the International Office.
Apply at: www.uni-frankfurt.de/masterstip.
Further information: Dr. Mathias Diederich, Hanna Reuther, International Office, Goethe University Frankfurt, Tel.: (069) 798-15090, email@example.com.
Frankfurt scientists reveal atomic details for one of Legionella’s enzymatic weapons and develop first inhibitor
FRANKFURT. Antimicrobial resistance (AMR) is a major medical problem worldwide, impacting both human health and economic well-being. A new strategy for fighting bacteria has now been reported in the latest online issue of Nature by a research group headed by Prof. Ivan Dikic at the Goethe University Frankfurt. The scientists revealed the molecular action mechanism of a Legionella toxin and developed a first inhibitor.
As resistance continues to spread, common infections such as pneumonia and salmonellosis are becoming increasingly harder to treat. Two factors drive the AMR crisis: human negligence in the use of antibiotics and a lack of truly novel antibiotics for more than 30 years. According to a recent report by the World Bank, by 2050, AMR may reduce the global gross domestic product by 1.1% to 3.8%, depending on which scenario plays out.
Scientific efforts are underway to achieve better control of microbial infections. One promising approach is to limit damage to host cells and tissues in the course of a bacterial infection by blocking the microbial processes that cause such damage. The laboratory of Ivan Dikic, Director of the Institute of Biochemistry II at Goethe University, has been working in this field for the past decade. As Dikic explains: “We believe we can find new treatments that complement conventional antibiotics by targeting specific groups of bacterial effectors with rationally designed drugs. In this way pathogenic damage can be decreased, which helps patients better tolerate bacterial infection. This is a relatively new field that is attracting more and more attention in the community.”
To prove that this strategy is a viable option for tackling bacteria, Dikic’s team studies Legionella, which are known to cause pneumonia and are especially dangerous for immunocompromised patients. Recently, the Frankfurt scientists were involved in identifying a novel enzymatic mechanism that Legionella bacteria use to seize control over their host cells. Dr. Sagar Bhogaraju, who works at Goethe University’s Buchmann Institute for Molecular Life Sciences as part of the Dikic team, reports: “We showed that Legionella enzyme SdeA acts as a toxic bacterial effector. It promotes the spreading of bacteria by targeting the ubiquitin system, one of the cell’s powerful protection mechanisms against stress.”
Ivan Dikic’s group has now reported a further breakthrough in the journal Nature: they succeeded in solving the atomic structure of SdeA. “The enzyme is truly unique and catalyses a reaction in a two-step mechanism”, comments Dr. Sissy Kalayil, who is one of the lead Frankfurt scientists on the project. “Our results are very exciting as they reveal atomic details of this mechanism, and make the rational design of inhibitors possible.” In their publication, the researchers also reveal how this bacterial effector probably chooses its victim proteins within the host cell, exerting its effect by attaching ubiquitin to them. They also developed a first inhibitor blocking this reaction in vitro. “Our basic discovery has allowed us to prove that these enzymes are druggable,” Dikic comments. “But it is early days. There is a long road ahead of us before we will be able to use this novel mechanism therapeutically. And we will surely not stop here.” Most likely, Legionella is not the only bacterium using this mechanism.
Ivan Dikic’s group is located at the Institute of Biochemistry II (Medical Faculty) and the Buchmann Institute for Molecular Life Sciences at Goethe University Frankfurt. The group investigates the role of ubiquitin in human diseases including cancer, amyotrophic lateral sclerosis and infectious diseases.
Publication: Kalayil S*, Bhogaraju S*, Bonn F, Shin D, Liu Y, Gan N, Basquin J, Grumati P, Luo Z-Q, Dikic I. Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination. Nature, Advanced Online Publication, DOI 10.1038/s41586-018-0145-8.
* Shared first authorship
In the same issue of Nature, there will be two articles published by the groups of Yue Feng (China) and Yuxin Mao (USA) which contribute additional details to the molecular mechanism of this unique enzyme (DOI 10.1038/s41586-018-0146-7 und 10.1038/s41586-018-0147-6
Link to images: www.uni-frankfurt.de/72116155
Caption: A detailed view of the 3D structure of the enzymatic active part of SdeA toxin (green). On the left, the essential catalytic surface is depicted in orange and the area for binding target proteins in purple. On the right, the amino acid residues involved in the reaction are highlighted. The detailed molecular picture now enables the design of suitable inhibitors. Source: Nature/Kalayil et al, Mai 2018
Information: Dr. Kerstin Koch, Institute of Biochemistry II, University Hospital Frankfurt, Phone: +49 69 6301 84250, firstname.lastname@example.org