Press releases – June 2020

FRANKFURT. An infection with Chagas disease is only possible in Latin America since the insect species that spread the disease only occur there. Scientists at Goethe University and the Senckenberg Society for Natural Research have now used ecological niche models to calculate the extent to which habitats outside of the Americas may also be suitable for the bugs. The result: climatically suitable conditions can be found in southern Europe for two kissing bug species; along the coasts of Africa and Southeast Asia the conditions are suitable for yet another species. The Frankfurt scientists therefore call for careful monitoring of the current distribution of triatomine bugs. (eLife DOI: 10.7554/eLife.52072)

The acute phase of the tropical Chagas disease (American Trypanosomiasis) is usually symptom-free: only in every third case does the infecting parasite (Trypanosoma cruzi) cause any symptoms at all, and these are often unspecific, such as fever, hives and swollen lymph glands. But the parasites remain in the body,  and many years later chronic Chagas disease can become life-threatening with pathological enlargement of the heart and progressive paralysis of the gastrointestinal tract. There is no vaccine for Chagas disease. The WHO estimates that 6 to 7 million people are infected worldwide, with the majority living in Latin America (about 4.6 million), followed by the USA with more than 300,000 and Europe with approximately 80,000 infected people.

Chagas parasites are transmitted by predatory blood-sucking bugs that ingest  the pathogen along with the blood. After a development period in the intestinal tract of the bugs, the parasites are shed in the bug's faeces. The highly infectious faeces are unintentionally rubbed into the wound by the extreme itching caused by the bug bite. Oral transmission by eating food contaminated with  triatomine bug faeces is also possible.

Researchers led by the Frankfurt parasitologists and infection biologists Fanny Eberhard and Professor Sven Klimpel have used niche models to investigate which climatic conditions in the world are suitable for Latin American kissing bugs. In particular, temperature and precipitation patterns were incorporated into the calculations on the climatic suitability of a region. The researchers were able to show that currently in addition to Latin America, Central Africa and Southeast Asia also have suitable habitats for triatomines. Two of the triatomine species, Triatoma sordida and Triatoma infestans, are now finding suitable habitats in temperate regions of southern Europe such as Portugal, Spain, France and Italy. Both triatomine species frequently transmit the dangerous parasites in Latin America and can be found inside or near houses and stables, where they get their nightly blood meals preferably from dogs, chickens and  humans.

Another triatomine species, Triatoma rubrofasciata, has already been detected outside Latin America. The model calculations by the Frankfurt scientists identify suitable habitats along large areas of the African and Southeast Asian coasts.

Professor Sven Kimpel explains: “There are people living in Europe who were infected with Chagas in Latin America and are unknowingly carriers of Trypanosoma cruzi. However, the parasite can currently only be transmitted to other people through untested blood preservations or by a mother to her unborn child. Otherwise, Trypanosoma cruzi requires triatomine bugs as intermediate hosts. And these bugs are increasingly finding suitable climatic conditions outside Latin America. Based on our data, monitoring programmes on the distribution and spreading of triatomine bugs  would therefore be feasible. Mandatory reporting of Chagas disease cases could also be helpful."

Publication: Fanny E. Eberhard, Sarah Cunze, Judith Kochmann, Sven Klimpel. Modelling the climatic suitability of Chagas disease vectors on a global scale. eLife 2020;9:e52072 doi: 10.7554/eLife.52072, https://elifesciences.org/articles/52072

An image may be downloaded here: http://www.uni-frankfurt.de/88953890

Caption: The triatomine or “kissing" bug Triatoma infestans. Credit: Dorian D. Dörge for Goethe University Frankfurt

Further information:
Prof. Dr. Sven Klimpel
Institute for Ecology, Evolution and Diversity, Goethe University
& Senckenberg Biodiversity and Climate Research Centre
Tel. +49 69 798 42237
E-Mail: Klimpel@bio.uni-frankfurt.de
https://www.bio.uni-frankfurt.de/43925886/Abt__Klimpel
http://www.bik-f.de/root/index.php?page_id=1224

Frankfurt and Ingelheim. Almost twenty years after deciphering the human genome, our understanding of human disease is still far from complete. One of the most powerful and versatile tools to better understand biology and disease-relevant processes is the use of well-characterized small chemical modulators of protein function. The new EUbOPEN consortium aims to develop high quality chemical tool compounds for 1,000 proteins (one third of the druggable proteins in the human body). It will enable unencumbered access to these research tools, thereby empowering academia and industry alike to explore disease biology and unlock the discovery of new drug targets and treatments.

The EUbOPEN consortium comprises 22 different partner organizations, including universities, research institutes, European Federation of Pharmaceutical Industries and Associations (EFPIA) members, and one small and medium-sized enterprise (SME). Goethe University Frankfurt and Boehringer Ingelheim are jointly leading the EUbOPEN consortium. Other partner organizations are Bayer AG, Diamond Light Source, EMBL-EBI, ETH Zürich, Fraunhofer IME, Georg-Speyer-Haus, Karolinska Institutet, Leiden University Medical Center, McGill University, Ontario Institute for Cancer Research, Pfizer, Royal Institute of Technology, Servier, the Structural Genomics Consortium, Takeda, University of Dundee, University of North Carolina, University of Oxford, and University of Toronto.

To interfere with the function of a protein in any given cell type, scientists need small chemical tools that affect the studied protein as specifically as possible, thereby avoiding unintended effects on other proteins. Therefore, there is an urgent need for selective and well-characterized chemical modulators for basic and applied research. Ideally, such tools would be available for every human protein. Moreover, these chemical modulators should be available to all researchers without restrictions on use, thus providing scientists with tools to better understand understudied proteins, thereby discovering possible links to disease.

The generation and dissemination of such high-quality and well-characterized research tools for a substantial fraction of the druggable human genome are the major goals of the newly formed public-private partnership “Enabling and Unlocking biology in the OPEN" (EUbOPEN). This large consortium was launched on 1 May 2020, with a total budget of 65.8 million euros covered by a grant from the Innovative Medicines Initiative (IMI) and cash/in-kind contributions from EFPIA companies and IMI Associated Partners and contributions from partners outside of Europe.

'EUbOPEN will provide the wider academic community with unencumbered access to the highest quality pharmacological tool compounds for a large number of novel targets, and seed a massive community target prioritization and deconvolution effort. The expected impact should be transformative', says Project Leader Adrian J. Carter, Boehringer Ingelheim.

'By the end of the project, we will have created the largest and most deeply characterised collection of chemical modulators of protein function that is openly available. The chemical tool sets and associated data will be a tremendous resource for academic science leading to the discovery of new biology and of novel disease modulating targets for the development of new medicines', adds Coordinator Stefan Knapp, Goethe University Frankfurt.

EUbOPEN will develop these compounds using new technologies and test them in well-characterized, disease-relevant human tissue assays in the areas of immunology, oncology and neuroscience. The project outputs, including chemogenomic library sets, chemical probes, assay protocols and associated research data will be made openly available to the research community without restriction.

The EUbOPEN project will form the foundation for future global efforts to generate chemical modulators for the entire druggable proteome and the developed new technologies will significantly shorten the lead optimization processes. The sustainability of the resources the project will be ensured through many partnerships for example with chemical vendors and biotech companies as well as online database providers. Internet: https://www.eubopen.org/

Innovative Medicines Initiative (IMI)

The IMI is Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe. IMI is a joint undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

For further details please visit: http://imi.europa.eu/

Further information:

Goethe-University Frankfurt:

Prof. Dr. Stefan Knapp
EUbOPEN Project Coordinator
Goethe University Frankfurt
knapp@pharmchem.uni-frankfurt.de

Dr. Markus Bernards
Science Communications
P  +49 (69) 798 12498
bernards@em.uni-frankfurt.de

Boehringer Ingelheim:

Dr. Adrian Carter
EUbOPEN Project Leader
Boehringer Ingelheim
adrian.carter@boehringer-ingelheim.com

Dr. Reinhard Malin
Head of Communications Innovation Unit
P: + 9 (6132) 77 90815
reinhard.malin@boehringer-ingelheim.com

FRANKFURT. For more than 100 years, we have been using X-rays to look inside matter, and progressing to ever smaller structures – from crystals to nanoparticles. Now, within the framework of a larger international collaboration on the X-ray laser European XFEL in Schenefeld near Hamburg, physicists at Goethe University have achieved a qualitative leap forward: using a new experimental technique, they have been able to “X-ray" molecules such as oxygen and view their motion in the microcosm for the first time.

“The smaller the particle, the bigger the hammer." This rule from particle physics, which looks inside the interior of atomic nuclei using gigantic accelerators, also applies to this research. In order to “X-ray" a two-atom molecule such as oxygen, an extremely powerful and ultra-short X-ray pulse is required. This was provided by the European XFEL which started operations in 2017 and is one of the the strongest X-ray source in the world

In order to expose individual molecules, a new X-ray technique is also needed: with the aid of the extremely powerful laser pulse the molecule is quickly robbed of two firmly bound electrons. This leads to the creation of two positively charged ions that fly apart from each other abruptly due to the electrical repulsion. Simultaneously, the fact that electrons also behave like waves is used to advantage. “You can think of it like a sonar," explains project manager Professor Till Jahnke from the Institute for Nuclear Physics. “The electron wave is scattered by the molecular structure during the explosion, and we recorded the resulting diffraction pattern. We were therefore able to essentially X-ray the molecule from within, and observe it in several steps during its break-up."

For this technique, known as “electron diffraction imaging", physicists at the Institute for Nuclear Physics spent several years further developing the COLTRIMS technique, which was conceived there (and is often referred to as a “reaction microscope"). Under the supervision of Dr Markus Schöffler, a corresponding apparatus was modified for the requirements of the European XFEL in advance, and designed and realised in the course of a doctoral thesis by Gregor Kastirke. No simple task, as Till Jahnke observes: “If I had to design a spaceship in order to safely fly to the moon and back, I would definitely want Gregor in my team. I am very impressed by what he accomplished here."

The result, which was published in the current issue of the renowned Physical Review X, provides the first evidence that this experimental method works. In the future, photochemical reactions of individual molecules can be studied using these images with their high temporal resolution. For example, it should be possible to observe the reaction of a medium-sized molecule to UV rays in real time. In addition, these are the first measurement results to be published since the start of operations of the Small Quantum Systems (SQS) experiment station at the European XFEL at the end of 2018.

Publication: 
Photoelectron diffraction imaging of a molecular breakup using an X-ray free-electron laser. Gregor Kastirke et al. Phys. Rev. X 10, 021052 https://doi.org/10.1103/PhysRevX.10.021052

Images may be downloaded at this link: http://www.uni-frankfurt.de/89043339

Caption: During the explosion of an oxygen molecule: the X-ray laser XFEL knocks electrons out of the two atoms of the oxygen molecule and initiates its breakup. During the fragmentation, the X-ray laser releases another electron out of an inner shell from one of the two oxygen atoms that are now charged (ions). The electron has particle and wave characteristics, and the waves are scattered by the other oxygen ion. The diffraction pattern are used to image the breakup of the oxygen molecules and to take snapshots of the fragmentation process (electron diffraction imaging). Credit: Till Jahnke, Goethe University Frankfurt

Further information:
Professor Till Jahnke
Institute for Nuclear Physics
Goethe University Frankfurt
Tel.: +49 69 798-47025
E-Mail: jahnke@atom.uni-frankfurt.de.

For European XFEL und SQS:
Dr. Michael Meyer
Holzkoppel 4
22689 Schenefeld
Tel.: 040 8998 5614
E-Mail: michael.meyer@xfel.eu

FRANKFURT. Speaking requires both sides of the brain. Each hemisphere takes over a part of the complex task of forming sounds, modulating the voice and monitoring what has been said. However, the distribution of tasks is different than has been thought up to now, as an interdisciplinary team of neuroscientists and phoneticians at Goethe University Frankfurt and the Leibniz-Centre General Linguistics Berlin has discovered: it is not just the right hemisphere that analyses how we speak – the left hemisphere also plays a role.

Until now, it has been assumed that the spoken word arises in left side of the brain and is analysed by the right side. According to accepted doctrine, this means that when we learn to speak English and for example practice the sound equivalent to “th", the left side of the brain controls the motor function of the articulators like the tongue, while the right side analyses whether the produced sound actually sounds as we intended.

The division of labour actually follows different principles, as Dr Christian Kell from the Department of Neurology at Goethe University explains: “While the left side of the brain controls temporal aspects such as the transition between speech sounds, the right hemisphere is responsible for the control of the sound spectrum. When you say 'mother', for example, the left hemisphere primarily controls the dynamic transitions between “th" and the vowels, while the right hemisphere primarily controls the sounds themselves." His team, together with the phonetician Dr Susanne Fuchs, was able to demonstrate this division of labour in temporal and spectral control of speech for the first time in studies in which speakers were required to talk while their brain activities were recorded using functional magnetic resonance imaging.

A possible explanation for this division of labour between the two sides of the brain is that the left hemisphere generally analyses fast processes such as the transition between speech sounds better than the right hemisphere. The right hemisphere could be better at controlling the slower processes required for analysing the sound spectrum. A previous study on hand motor function that was published in the scientific publication “elife" demonstrates that this is in fact the case. Kell and his team wanted to learn why the right hand was preferentially used for the control of fast actions and the left hand preferred for slow actions. For example, when cutting bread, the right hand is used to slice with the knife while the left hand holds the bread.

In the experiment, scientists had right-handed test persons tap with both hands to the rhythm of a metronome. In one version they were supposed to tap with each beat, and in another only with every fourth beat. As it turned out, the right hand was more precise during the quick tapping sequence and the left hemisphere, which controls the right side of the body, exhibited increased activity. Conversely, tapping with the left hand corresponded better with the slower rhythm and resulted in the right hemisphere exhibiting increased activity.

Taken together, the two studies create a convincing picture of how complex behaviour – hand motor functions and speech – are controlled by both cerebral hemispheres. The left side of the brain has a preference for the control of fast processes while the right side tends to control the slower processes in parallel.

Publications:
Floegel M, Fuchs S, Kell CA (2020) Differential contributions of the two cerebral hemispheres to temporal and spectral speech feedback control. Nature Communications, 11:2839. https://doi.org/10.1038/s41467-020-16743-2

Pflug A, Gompf F, Muthuraman M, Groppa S, Kell CA (2019) Differential contributions of the two human cerebral hemispheres to action timing. eLife, 8:48404 https://doi.org/10.7554/eLife.48404

Further information: Dr. Christian Kell, Cognitive Neuroscience Group, Clinic for Neurology, Goethe University Frankfurt/ University Hospital Frankfurt, Tel.: +49 69 6301-6395, E-mail: c.kell@em.uni-frankfurt.de