66 million euros to generate open-access chemical tools
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/
Prof. Dr. Stefan Knapp
EUbOPEN Project Coordinator
Goethe University Frankfurt
Dr. Markus Bernards
P +49 (69) 798 12498
Dr. Adrian Carter
EUbOPEN Project Leader
Head of Communications Innovation Unit
P: + 9 (6132) 77 90815
New experimental technique with Goethe University’s reaction microscope allows “X-ray” of individual molecules
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.
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
Professor Till Jahnke
Institute for Nuclear Physics
Goethe University Frankfurt
Tel.: +49 69 798-47025
For European XFEL und SQS:
Dr. Michael Meyer
Tel.: 040 8998 5614
Frankfurt neuroscientists: Both hemispheres of the brain make a unique contribution to speech control – new research casts doubt on current doctrine
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.
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: email@example.com
Unique long-term videos show the bee nursery in the hive
FRANKFURT. A newly developed video technique has allowed scientists at Goethe University Frankfurt at the Bee Research Institute of the Polytechnical Society to record the complete development of a honey bee in its hive for the first time. It also led to the discovery that certain pesticides – neonicotinoids – changed the behaviour of the nurse bees: researchers determined that they fed the larvae less often. Larval development took up to 10 hours longer. A longer development period in the hive can foster infestation by parasites such as the Varroa mite (Scientific Reports, DOI 10.1038/s41598-020-65425-y).
Honey bees have very complex breeding behaviour: a cleaning bee cleans an empty comb (brood cell) of the remains of the previous brood before the queen bee lays an egg inside it. Once the bee larva has hatched, a nurse bee feeds it for six days. Then the nurse bees caps the brood cell with wax. The larva spins a cocoon and goes through metamorphosis, changing the shape of its body and developing a head, wings and legs. Three weeks after the egg was laid, the fully-grown bee hatches from the cocoon and leaves the brood cell.
Using a new video technique, scientists at
Goethe University Frankfurt have now succeeded for the first time in recording
the complete development of a honey bee in a bee colony at the Bee Research
Institute of the Polytechnical Society. The researchers built a bee hive with a
glass pane and were thus able to film a total of four bee colonies
simultaneously over several weeks with a special camera set-up. They used deep red
light so that the bees were not disturbed, and recorded all the movements of
the bees in the brood cells.
The researchers were particularly interested in the nursing behaviour of the nurse bees, to whose food (a sugar syrup) they added small amounts of pesticides known as neonicotinoids. Neonicotinoids are highly effective insecticides that are frequently used in agriculture. In natural environments, neonicotinoids arrive in bee colonies through nectar and pollen collected by the bees. It is already known that these substances disturb the navigational abilities and learning behaviour of bees. In a measure criticised by the agricultural industry, the European Union has prohibited the use of some neonicotinoids in crop cultivation.
Using machine learning algorithms developed by the scientists together with colleagues at the Centre for Cognition and Computation at Goethe University, they were able to evaluate and quantify the nursing behaviour of the nurse bees semi-automatically. The result: even small doses of the neonicotinoids Thiacloprid or Clothianidin led to the nurse bees feeding the larva during the 6-day larval development less frequently, and consequently for a shorter daily period. Some of the bees nursed in this manner required up to10 hours longer until the cell was capped with wax.
“Neonicotinoids affect the bees' nervous systems by blocking the receptors for the neurotransmitter acetylcholine," explains Dr Paul Siefert, who carried out the experiments in Professor Bernd Grünewald's work group at the Bee Research Institute Oberursel. Siefert: “For the first time, we were able to demonstrate that neonicotinoids also change the social behaviour of bees. This could point to the disruptions in nursing behaviour due to neonicotinoids described by other scientists." Furthermore, parasites such as the feared Varroa mite (Varroa destructor) profit from an extended development period, since the mites lay their eggs in the brood cells shortly before they are capped: if they remain closed for a longer period, the young mites can develop and multiply without interruption.
However, according to Siefert, it still remains to be clarified whether the delay in the larval development is caused by the behavioural disturbance of the nurse bee, or whether the larvae develop more slowly because of the altered jelly. The nurse bees produce the jelly and feed it to the larvae. “From other studies in our work group, we know that the concentration of acetylcholine in the jelly is reduced by neonicotinoids," says Siefert. “On the other hand, we have observed that with higher dosages, the early embryonal development in the egg is also extended – during a period in which feeding does not yet occur." Additional studies are needed to determine which factors are working together in these instances.
In any case, the new video technique and the evaluation algorithms offer great potential for future research projects. In addition to feeding, behaviours for heating and construction were also able to be reliably identified. Siefert: “Our innovative technology makes it possible to gain fundamental scientific insights into social interactions in bee colonies, the biology of parasites, and the safety of pesticides."
Publication: Paul Siefert, Rudra Hota, Visvanathan Ramesh, Bernd Grünewald. Chronic within-hive video recordings detect altered nursing behaviour and retarded larval development of neonicotinoid treated honey bees. Sci. Rep. 10, 8727 (2020).
Video: Development of a bee larva https://www.nature.com/articles/s41598-020-65425-y (Supplementary Material)
Images may be downloaded here: http://www.uni-frankfurt.de/88682581
Figure 1: Diagram/monitoring of brood cells – side view of the construction and camera view of the brood area. The brood area of the bees was filmed with a camera (green) through a dome lighting (grey). The specially designed hive (brown) was only 2.4 cm wide, so that the bees would raise young as quickly as possible (right). Credit: Paul Siefert/Bee Research Institute Oberursel/Goethe University Frankfurt
Figure. 2 Excerpts from the video of the development of a worker bee. Above left: The queen lays an egg (arrow) in the cell. The growing larva (arrow) is fed with jelly. Below left: the metamorphosis takes about one hour and includes the rupture of the larval skin (arrow); the pupa is beneath it. Finally, the adult bee hatches out of the cell. Credit: Paul Siefert/Bee Research Institute Oberursel/Goethe University Frankfurt
Dr Paul Siefert
Bee Research Institute Oberursel
Subsidiary of the Polytechnical Society Frankfurt am Main,
Faculty of Biosciences
Goethe University Frankfurt am Main
Tel.: +49 6171 21278
Two research aircraft investigate reduced concentrations of pollutants in the air
FRANKFURT. The COVID-19 pandemic is not only affecting almost every aspect of our daily lives, but also the environment. A German team including atmosphere researchers around Prof. Joachim Curtius (Goethe University Frankfurt) now wants to find out how strong these effects are on the atmosphere. Over the next two weeks, as part of the BLUESKY research programme, the scientists led by the Max Planck Institute for Chemistry and the German Aerospace Center (Deutsches Zentrum für Luft- und Raumfahrt; DLR) will measure concentrations of trace gases and pollutants in the air over European urban areas and in the flight corridor to North America. The aim of these research missions is to investigate how reduced emissions from industry and transport are changing atmospheric chemistry and physics.
A German research team now wants to make rapid use of this unusual situation for the BLUESKY project. Scientists from DLR, the Max Planck Institute for Chemistry, Goethe University Frankfurt, and the research centres at Jülich and Karlsruhe intend to use two DLR research aircraft to conduct a globally unique investigation into the resulting changes in Earth's atmosphere for the first time. DLR’s HALO and Falcon research aircraft have been equipped with highly specialised instrumentation and will fly over Germany, Italy, France, Great Britain and Ireland in the course of the next two weeks. They will also fly over the North Atlantic, along the flight corridor to North America.
“DLR is deploying part of its unique research aircraft fleet to exploit an almost unique opportunity. During these missions, the atmosphere will be analysed in a state that could be achieved in the future with sustainable management of human activities. We will observe how the environment changes with the ramp-up of industrial activities. This will give us an entirely new perspective on the anthropogenic influence on Earth’s atmosphere,” explains Rolf Henke, DLR Executive Board Member responsible for aeronautics research. “Together with our partners, we are making a significant contribution to redefining humankind’s activities once the pandemic is under control.”
Coordinated research flights with two measurement aircraft
Jos Lelieveld, Director of the Max Planck Institute for Chemistry, wants to use the BLUESKY missions to clarify whether there is a correlation between the clear blue sky during the lockdown and the prevalence of aerosol particles in the atmosphere. “The unique blue sky of recent weeks cannot be explained by meteorological conditions and the decrease in emissions near the ground. Aircraft may have a greater impact on the formation of aerosol particles than previously thought,” says the atmospheric researcher, who is the Scientific Director of the HALO flights. Aerosols, microscopic particles in the air that also influence cloud formation, are finely distributed. They scatter and absorb solar radiation and thus also have an impact on the climate, because they influence the radiation balance of the atmosphere. Aerosols are created, amongst other ways, during the combustion of fossil fuels.
Christiane Voigt, Head of the Cloud Physics Department at the DLR Institute of Atmospheric Physics and Scientific Director of the Falcon flights, also sees a unique opportunity with BLUESKY. “The current state of the atmosphere represents a kind of ‘zero point’ for science. We will be able to measure a reference atmosphere that is only slightly polluted with emissions from industry and transport, including aviation. This gives us a unique opportunity to better understand the effects of the anthropogenic emissions prior to the shutdown.” The atmospheric physicist emphasises that, only through the cooperation of all the partners, was it possible to plan and implement the scientifically and logistically highly complex missions at very short notice.
Emissions from air transport, industry and road traffic in urban areas
Voigt and her colleagues believe that the BLUESKY data will provide a clearer picture of anthropogenic influences on the composition of Earth’s atmosphere. With the equipment on board both research aircraft, the BLUESKY scientists are investigating aircraft emissions such as nitrogen oxides, sulphur dioxide and aerosols at cruising altitude, in addition to the few remaining contrails. Among other things, they want to find out how much these emissions have decreased over Europe and the North Atlantic flight corridor. Approximately 30,000 aircraft fly over Europe every day, with correspondingly significant emissions. The reduced air traffic will allow more flexible flight routes for the measurements.
In addition, the researchers want to investigate the reduced emission plumes from urban areas and clarify how emissions are distributed at the atmospheric boundary layer. For example, the BLUESKY scientists plan to fly over the Ruhr area and the regions around Frankfurt am Main, Berlin and Munich. Flights over the Po Valley in Italy and around Paris and London are also planned. “Close to cities and conurbations, we will approach the atmospheric boundary layer at an altitude of one to two kilometres, since emissions from road traffic and industry are concentrated there,” explains Jos Lelieveld. “We are interested in how much the concentrations of sulphur dioxide, nitrogen oxides, hydrocarbons and their chemical reaction products, as well as ozone and aerosols, have changed.” He is also very proud that the team is the first in the world to implement a measurement campaign of this type.
Rapid preparations for flights – with special infection control rules
In recent weeks, two DLR research aircraft –measuring the Falcon 20E and the Gulfstream G550 HALO – have been successfully converted at short notice for the BLUESKY missions. The conversions were carried out at the DLR Flight Operations Facility in Oberpfaffenhofen. “Numerous instruments have had to be installed and adapted, and the aircraft modified for the upcoming missions,” says Burkard Wigger, Head of DLR Flight Experiments. “Close cooperation between the various scientific organisations has made it possible for these two research aircraft to operate simultaneously under the challenging conditions resulting from the Coronavirus pandemic.”
The preparation, execution and follow-up of the flights is being carried out in accordance with the current rules regarding personal interactions and infection control. Joint flights by Falcon and HALO are planned until the first half of June. The evaluation of the data and the analysis of the results will then take several months. The analysis will include comparative data from previous HALO research flight campaigns on air traffic emissions and emissions from major cities and conurbations.
About HALO: The High Altitude and Long Range (HALO) research aircraft is a joint initiative of German environmental and climate research institutions. HALO is supported by grants from the Federal Ministry of Education and Research (BMBF), the German Research Foundation (DFG), the Helmholtz Association of German Research Centres, the Max Planck Society (MPG), the Leibniz Association, the Free State of Bavaria, the Karlsruhe Institute of Technology (KIT), the Forschungszentrum Jülich and the German Aerospace Center (DLR).
More information: Prof. Joachim Curtius, Institute for Atmospheric and Environmental Sciences, Goethe University Frankfurt, Phone: +49 (0)69 798-40258, firstname.lastname@example.org