Press releases

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, rezzolla@fias.uni-frankfurt.de.

ExaHyPE Projekt: http://exahype.eu/

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, m.diederich@em.uni-frankfurt.de.

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, k.koch@em.uni-frankfurt.de

Current news about science, teaching, and society in GOETHE-UNI online (www.aktuelles.uni-frankfurt.de)

FRANKFURT. Due to global trade and tourism, mosquitoes - transmitters of dangerous infectious diseases - have spread to almost every part of the world. Moreover, climate change promotes the spread of species that thrive under warmer temperatures even further. Scientists at the Goethe University and the Senckenberg Gesellschaft für Naturforschung have now compared the ecological niches of the Asian tiger mosquito and the yellow fever mosquito on various continents with the following result: “Due to its longer invasion time span of 300 to 400 years, the yellow fever mosquito has almost completely filled its niches in non-native areas, whereas the Asian tiger mosquito, with a shorter invasion time span of 30 to 40 years, has not yet arrived in all regions where they would find a suitable environment,” says Prof. Sven Klimpel.

“Over the next one to five decades, infectious diseases transmitted through vectors will increase” concludes Sven Klimpel’s team at the Goethe University and the Senckenberg Gesellschaft für Naturforschung. Vectors transmit agents that cause infectious diseases from a host to another organism without contracting the disease themselves. Many known vector species are native to tropical and subtropical regions. If vector species are established in a new area together with a disease agent, the area of risk for the associated disease will expand correspondingly.

Two prominent examples of vectors are the Asian tiger mosquito (Aedes albopictus) and the yellow fever mosquito (Aedes aegypti). The yellow fever mosquito is the main vector of the yellow fever virus, the dengue virus, the Zika virus and several other viral diseases. The tiger mosquito can also transmit the Zika virus and the dengue virus, but transmits other disease agents as well, such as the West Nile virus and the Chikungunya virus. These two medically relevant vectors are the focus of the current study in “Scientific Reports”.

The yellow fever mosquito, originally native to Africa, began to spread throughout the world 300 to 400 years ago – presumably with the expansion of sugar cane plantations and slave trade. The tiger mosquito, which today is considered one of the 100 worst invasive species, originally comes from South and Southeast Asia. Over the past several decades, it has been introduced and spread by trade and tourism, especially by the trade of automobile tires and lucky bamboo (Dracaena spp.). For example, tiger mosquito eggs, larva and pupae were transported great distances by sea, surviving in small water puddles inside used automobile tires, or in water containers for lucky bamboo.

In their study, the scientists investigated the ecological niches of both species in their native and non-native range, i.e., the totality of environmental conditions in which a species can occur. In their new ranges of distribution, mosquitoes can encounter different environmental conditions than in their native ranges. Invasive mosquito species are said to be especially quick to adapt to new climatic conditions. The scientists, however, found no evidence to support this. Both species occupy a broad niche and occur in a large number of different environmental conditions in their native ranges. Since similar climatic conditions prevail in the new distribution ranges, worldwide expansion cannot be explained by a niche expansion through adaptation, although local adaptation and genetic changes in species’ traits cannot be ruled out.

The scientists were, however, able to identify a difference between the two species: that time plays an important role in the expansion or invasion of a species. With its longer time span of invasion, the yellow fever mosquito almost completely fills its niche in the new, non-native distribution ranges; i.e. it occurs under many climatic conditions that also exist in its native distribution range. 

The Asian tiger mosquito is a different case. In the new distribution ranges, it does not (yet) occur in all habitats that offer suitable climatic conditions. The researchers therefore predict a further expansion potential for this species in the future. Klimpel sums up: “The Asian tiger mosquito can already be found in nearly all southern European countries, and due to its broad niche, it will inevitably spread and establish itself in northern Europe as well. Further exotic mosquito species such as Aedes japoniucs (East Asian bush mosquito), Aedes koreicus or Aedes atropalpus will follow - or have already arrived - in Central Europe.“

Images may be downloaded at: www.uni-frankfurt.de/72048458

• Image 1: Worldwide expansion of the two invasive mosquito species a) Asian tiger mosquito (Aedes albopictus) and b) yellow fever mosquito (Aedes aegypti) and studied areas
• Image 2: Asian tiger mosquito (Aedes albopictus) caught in Rovinj (Croatia).
• Image 3: Habitus of a female Asian tiger mosquito (Aedes albopictus).

Copyright: photos from Dorian D. Dörge (Goethe University)

Publication:

Sarah Cunze, Judith Kochmann, Lisa K. Koch, Sven Klimpel: Niche conservatism of Aedes albopictus and Aedes aegypti - two mosquito species with different invasion histories, in Scientific Reports, DOI:10.1038/s41598-018-26092-2

Information: Prof. Dr. Sven Klimpel, Institute for Ecology, Evolution and Diversity, Faculty of Biological Sciences, Riedberg Campus Frankfurt am Main, Tel. -49 69 798-42237, Klimpel@bio.uni-frankfurt.de

FRANKFURT. Not everyone person who has a “cancer gene” will inevitably develop this disease in their lifetime. Thanks to a new area of research called epigenetics, we now know that many genes are only read under certain circumstances. Prof. Stefan Knapp from the Institute of Pharmaceutical Chemistry and Buchmann Institute of Molecular Life Sciences at the Goethe University not only researches the underlying mechanisms, he also developed small molecules that inhibit the derailment of gene expression in cancer. Now he has been elected as one of 62 new members in the European scientific organization for molecular biology, EMBO, joining a group of more than 1800 of the best researchers in Europe and around the world.

“I am delighted that I have been elected to the EMBO society and I am looking forward working with this group of outstanding scientists to advance research, exchange new ideas, and promote science in society”, says Stefan Knapp.

Prof Knapp has made seminal contributions to the elucidation of structural mechanisms of the regulation of proteins that play key roles in signal transduction. This in turn led to a detailed description of protein family specific regulatory mechanisms and the elucidation of substrate recognition processes. Based on these findings, he developed a large array of new small molecule inhibitors, in particular highly specific inhibitors for epigenetic reader domains.

The first potent inhibitor developed by Prof Knapp and colleagues validated epigenetic reader domains as target for cancer therapy which led to a diverse set of highly selective inhibitors targeting these proteins. Prof Knapp’s work has provided new insights into chromatin biology and paved the way for more than 25 clinical trials in this new area of drug discovery.

Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996). In 1999, he joined the Pharmacia Corporation, where he worked for five years as a principal research scientist in structural biology and biophysics. In 2004, he set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He has been the CSO of the newly founded SGC node at the Goethe-University Frankfurt since 2017.

About EMBO // EMBO is an organization of more than 1800 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

Further Information: Prof. Stefan Knapp, Institute of Pharmaceutical Chemistry and Buchmann Institute of Molecular Life Sciences, Faculty of Biochemistry, Chemistry and Pharmacy, Tel.: +49 (0) 69 798-29871, Knapp@pharmchem.uni-frankfurt.de