Press releases

A short ten months after Goethe University and Frankfurt University Hospital first called for donations, the Goethe Coronavirus Fund has passed the targeted 5 million euro mark. The idea of the Goethe Coronavirus Fund came about in the first days of the pandemic: researchers require immediate and unbureaucratic support in order to make their contribution to overcoming the coronavirus crisis. More than 2000 private individuals, foundations and companies have meanwhile supported the goal of joining forces and providing competent help.

FRANKFURT. “Making a donation to research helped me overcome a feeling of helplessness during the first days of the coronavirus crisis,” says Raina Jockers, one of the more than 2000 donors for the Goethe Coronavirus Fund, explaining her motivation. The feelings of the Goethe University graduate are undoubtedly shared by many. The majority of donors contributed between 10 and 100 euros to the fund. The smallest donation came from the donation of bonus points from the “payback” programme and amounted to 2 cents; the largest was almost one million euros. Eight donors gave sums of more than 100,000 euros.

Using the non-profit online fundraising platform betterplace.org for the first time, the university’s call for donations reached even beyond Frankfurt citizens and foundations and companies from the Rhine-Main area, with donations coming in from Hamburg, Munich and even the USA. The fundraising platform also reported regularly on the work of the scientists, which may have motivated some donors to stick with it: one anonymous donor contributed 20 euros to the fund every month.

“In the pandemic, we wanted to help with what we do best: with our research,” says Professor Manfred Schubert-Zsilavecz, Goethe University Vice President. “So we simply jumped in at the deep end with our fundraising campaign and set ourselves an ambitious target: 5 million euros in donations. The fact that we have reached the 5 million euro mark in less than a year after our first call for donations makes us deeply grateful. Many private donors, as well as foundations and companies have been extremely generous. They funded research that helps us all,  keeping others in mind during this pandemic. This should really encourage us for the long road ahead.”

The Goethe Coronavirus Fund provided researchers at Goethe University and Frankfurt University Hospital with start-up support. Many of them have in the meantime raised additional funds for research having to do with SARS-CoV-2. The virologist Professor Sandra Ciesek and the infectologist Professor Maria Vehreschild, for example, are today part of the EU-funded CARE Consortium. Sandra Ciesek’s successes in drug research have made her one of the most prominent coronavirus researchers in Germany. Maria Vehreschild was one of the first to systematically collect clinical data and samples from COVID-19 patients and supplied her samples to vaccine and drug researchers throughout Germany; in the meantime, her database has been merged into a Germany-wide biobank.

But researchers from the social sciences and humanities have also profited from the Goethe Coronavirus Fund. More than 40 projects are now being funded – including the coronavirus crisis hotline, and studies by psychologist Professor Ulrich Stagnier on the psychological consequences of the pandemic.

The latest project supported by the Coronavirus Fund is dedicated to the work situation of healthcare workers and doctors in COVID-19 care in Hessian hospitals who are under particular strain. The cooperation project of the University Hospital Frankfurt and the Protestant University of Applied Sciences in Darmstadt first examines the effects on the employees. The results will be used to make recommendations for managers and healthcare workers, as well as concrete options for workplace health promotion. The evaluation of the first sub-study of the project is currently underway.

Further donations possible at: https://www.goethe-corona-fonds.betterplace.org and
through the donation account: Landesbank Hessen-Thüringen
IBAN: DE95 5005 0000 0001 0064 10
Reason for payment: Goethe-Corona-Fonds 

Scientists at Goethe University Frankfurt, together with colleagues from Darmstadt, Heidelberg, Oxford and Dundee (UK), have investigated how the fit of potent inhibitors to their binding sites can be optimised so that they engage longer with their target proteins. Long target residency has been associated with more efficient pharmacological responses for instance in cancer therapy. The result: High resolution structures revealed that when the interaction between the inhibitors and the target proteins lasts particularly long, the target proteins "nestle" against the inhibitors. In future, the researchers want to use computer simulations to predict the residence time of inhibitors during drug development.

FRANKFURT. Many anti-cancer drugs block signals in cancer cells that help degenerated cells to multiply uncontrollably and detach from tissue. For example, blocking the signalling protein FAK, a so-called kinase, causes breast cancer cells to become less mobile and thus less likely to metastasise. The problem is that when FAK is blocked by an inhibitor, the closely related signalling protein PYK2 becomes much more active and thus takes over some of FAK's tasks. The ideal would therefore be an inhibitor that inhibits both FAK and PYK2 in the same way for as long as possible.

An international team led by the pharmaceutical chemist Prof. Stefan Knapp from Goethe University has investigated a series of specially synthesised FAK inhibitors. All inhibitors bound to the FAK protein at about the same rate. However, they differed in the duration of binding: The most effective inhibitor remained bound to the FAK signalling protein the longest.

Using structural and molecular biological analyses as well as computer simulations, the research team discovered that binding of inhibitors that remain in the FAK binding pocket for a long time induce a structural change. Thus, through binding of these inhibitors, FAK changes its shape and forms a specific, water-repellent structure at contact sites with the inhibitor, comparable to an intimate embrace.

The closely related protein PYK2, on the other hand, remained comparatively rigid, and although the most effective FAK inhibitor also blocked PYK2, its effect was significantly weaker due to quickly dissociating inhibitors from the binding site. Interestingly, computer simulations were able to predict the kinetics of binding very well, providing a method for accurate simulation of drug dissociation rates for future optimisation of drug candidates.   

Prof. Stefan Knapp explains: "Because we now have a better understanding of the molecular mechanisms of the interaction of potent inhibitors of these two kinases, we hope to be able to use computer simulations to better predict drug residence times of inhibitors and drugs candidates in the future. So far, little attention has been paid to the kinetic properties of drug binding. However, this property has now emerged as an important parameter for the development of more effective drugs that are designed to inhibit their target proteins - as in the case of FAK and PYK2 - not only potently but also for a long time."

Publication: Benedict-Tilman Berger, Marta Amaral, Daria B. Kokh, Ariane Nunes-Alves, Djordje Musil, Timo Heinrich, Martin Schröder, Rebecca Neil, Jing Wang, Iva Navratilova, Joerg Bomke, Jonathan M. Elkins, Susanne Müller, Matthias Frech, Rebecca C. Wade, Stefan Knapp: Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2. Cell Chemical Biology https://doi.org/10.1016/j.chembiol.2021.01.003

This work was carried out within the framework of the public-private partnership K4DD (Kinetics for Drug Discovery) of the Innovative Medicinces Initiatives (IMI). https://www.k4dd.eu/home/

Images for download:
Picture with and without text: http://www.uni-frankfurt.de/96999809

Caption:
Upper part: Long residence time. An inhibitor (left: stick model) binds to the signal molecule FAK (right: part oft the FAK protein depicted as calotte model with spheres). The structural change of FAK causes hydrophobic contacts (yellow, so-called DFG motif) and a long-lasting engagement.
Lower part: Short residence time. PYK2 signal protein does not change its structure upon inhibitor binding, thus resulting in a fast inhibitor dissociation. Graphics: Knapp Laboratory, Goethe University Frankfurt

Further information:
Professor Stefan Knapp
Institute for Pharmaceutical Chemistry
Goethe University Frankfurt
Germany
knapp@pharmchem.uni-frankfurt.de

Bacteria act in groups to accomplish feats that are impossible to achieve if a single bacterium acts alone. For example, pathogenic bacteria act collectively to synthesize toxins to attack the host and to encase themselves in a shield that protects them from the host immune system and allows them to resist antibiotic treatment. To do this, bacteria communicate with each other with chemical “words", count their numbers, and act in synchrony when they have sufficient cell numbers for success. The award winners have discovered the dictionary and syntax underlying bacterial communication, opening up new and unprecedented opportunities to fight bacterial infections.

FRANKFURT am MAIN. Two American scientists, Bonnie L. Bassler and Michael R. Silverman, receive the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize, which is endowed with 120,000 €. Bassler is Professor at Princeton University and a Howard Hughes Medical Institute Investigator, Michael R. Silverman is Emeritus Professor of the Agouron Institute in La Jolla. The two researchers are honoured for their ground-breaking discoveries concerning bacterial "quorum sensing", which refers to sophisticated systems of cell-to-cell communication that bacteria use to coordinate group behaviours. The award ceremony in St. Paul's Church, which is traditionally held on March 14, Paul Ehrlich's birthday, has been postponed due to the Coronavirus pandemic. Instead, Bassler and Silverman will receive the award at the ceremony in 2022.

"Silverman and Bassler have shown that, as for multicellular organisms, collective behaviour is the rule among bacteria, rather than the exception," wrote the Scientific Council in substantiating its decision. "Bacteria talk to each other, they eavesdrop on other bacteria, and they may even join forces. But: This ubiquitous chitchat, whose molecular underpinnings were discovered by Bassler and Silverman, also represents a previously unappreciated Achilles' heel in combating harmful microbes. Instead of killing bacteria with antibiotics, substances may be developed that interfere with bacterial communication effectively reducing their collective fitness. The prize-winners' research thus has considerable relevance for medicine".

Bacteria are extremely communicative. They send and receive chemical messages to find out whether they are alone or if additional members of their or other species are present in the vicinal community. To take a census of cell numbers, bacteria produce and release chemical signal molecules that accumulate in step with increasing cell numbers. When a threshold level of the chemical signal is achieved, the bacteria detect its presence. In response to it, in unison, bacteria undertake behaviours that are only productive when carried out in synchrony by the group, but not when enacted by a single bacterium acting in isolation. This chemical communication process is called quorum sensing and it controls hundreds of collective activities across the bacterial kingdom.

In the 1980s, Silverman discovered the first quorum-sensing circuit in the bioluminescent marine bacterium Vibrio fischeri. He identified the genes and proteins enabling production and detection of the extracellular signal molecule. He defined how the components functioned to promote collective behaviour. In the case of Vibrio fischeri, group-wide behaviour is the production of blue-green bioluminescence. Today, we know that quorum sensing is the norm in the bacterial world. Indeed, there are thousands of bacterial species that possess genes nearly identical to those discovered by Silverman. In all of these cases, these components allow bacteria to engage in group behaviours.

In the early 1990s, Bonnie Bassler proved that bacteria were “multilingual" and that they conversed with multiple chemical signal molecules. One communication molecule that Bassler discovered and named autoinducer- 2 enables bacteria to communicate across species boundaries. She went on to demonstrate that bacteria use quorum-sensing-mediated communication to differentiate self from other, showing that a sophisticated trait thought to be the purview of higher organisms, in fact, evolved in bacteria billions of years ago. In recent years, Bassler has shown that quorum sensing transcends kingdom boundaries as viruses and host cells, including human cells, engage in this ubiquitous chit-chat. She and other researchers also demonstrated that pathogenic bacteria rely on quorum sensing to be virulent. Bassler developed anti-quorum-sensing strategies that, in animal models, halt infection from bacterial pathogens of global significance.

“The full significance of the discoveries of the two laureates for microbiology and medicine has only recently been recognized," says Professor Thomas Boehm, Director at the Max Planck Institute for Immunobiology and Epigenetic and Chairman of the Scientific Council. "Decades of meticulous and painstaking work, showed that essentially all bacteria master the art of cell-to-cell communication," says Boehm. "What began with work on Vibrio fischeri and Vibro harveyi led to a fundamental change in perspective in bacteriology, and now opens up new and unprecedented opportunities in dealing with antibiotic resistance".

Short biography Professor Dr. Bonnie L. Bassler Ph.D. (58).

Bonnie Bassler is a microbiologist. She studied biochemistry at the University of California at Davis and received her Ph.D. from the Johns Hopkins University in Baltimore. She joined the laboratory of Michael Silverman at the Agouron Institute in La Jolla as a postdoctoral fellow in 1990. She has been at Princeton University since 1994. Bonnie Bassler is a member of the National Academy of Sciences, the National Academy of Medicine, and the Royal Society. She is a researcher at the Howard Hughes Medical Institute and Squibb Professor and Chair of the Department of Molecular Biology at Princeton University. President Obama appointed her to a six-year term on the United States National Science Board. She has received more than twenty prestigious national and international awards.

Short biography Professor Michael R. Silverman, Ph.D. (77).

Michael Silverman is a microbiologist. He studied chemistry and bacteriology at the University of Nebraska at Lincoln and received his Ph.D. in 1972 from the University of California at San Diego. During the period from 1972-1982, Silverman made seminal contributions to the understanding of bacterial motility and chemotaxis. From 1982 until his retirement, he worked at the Agouron Institute in La Jolla, of which he is a co-founder.

The Paul Ehrlich and Ludwig Darmstaedter Prize
The Paul Ehrlich and Ludwig Darmstaedter Prize is traditionally awarded on Paul Ehrlich's birthday, March 14, in the Paulskirche, Frankfurt. It honors scientists who have made significant contributions in Paul Ehrlich's field of research, in particular immunology, cancer research, microbiology, and chemotherapy. The Prize, which has been awarded since 1952, is financed by the German Federal Ministry of Health, the State of Hesse, the German association of research-based pharmaceutical company vfa e.V. and specially earmarked donations from the following companies, foundations and organizations: Else Kröner-Fresenius-Stiftung, Sanofi-Aventis Deutschland GmbH, C.H. Boehringer Pharma GmbH & Co. KG, Biotest AG, Hans und Wolfgang Schleussner-Stiftung, Fresenius SE & Co. KGaA, F. Hoffmann-LaRoche Ltd., Grünenthal GmbH, Janssen-Cilag GmbH, Merck KGaA, Bayer AG, Holtzbrinck Publishing Group, AbbVie Deutschland GmbH & Co. KG, die Baden-Württembergische Bank, B. Metzler seel. Sohn & Co. and Goethe-Universität. The prizewinners are selected by the Scientific Council of the Paul Ehrlich Foundation.

The Paul Ehrlich Foundation
The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president of the German Research Foundation, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Thomas Boehm, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.

Further information:
You can obtain selected publications, the list of publications and a photograph of the laureate from Dr. Hildegard Kaulen, phone: +49 (0)6122/52718, email: h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de

Background on the award of the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize to Professor Bonnie L. Bassler, Ph.D. and Professor Michael R. Silverman, Ph.D.

The course for organ health is set in the early embryo. This year's laureate has shown that specialized immune cells from the yolk sac accompany organ development and contribute to maintaining their health throughout life. For Elvira Mass, impaired function of these immune cells might cause many diseases.

Frankfurt am Main. Developmental biologist Professor Elvira Mass, Ph.D. from the Life and Medical Sciences Institute (LIMES) at the University of Bonn, receives the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers, which is endowed with €60,000. The award ceremony in Paulskirche, which is traditionally held on March 14th, Paul Ehrlich's birthday, has been canceled this year due to the coronavirus pandemic. Elvira Mass will be honored next year together with the award winners of 2022.

For organs to stay healthy and functional, they must be constantly surveilled for abnormalities. Until a few years ago, it was believed that this task is performed by immune cells originating from the bone marrow. In a series of elegant genetic labelling experiments, Mass has shown that these cells are mainly yolk sac-derived progenitor cells that migrate to the developing organs, where they immediately differentiate and self-maintain for a lifetime. The reason for their longevity is still a mystery. These immune cells are referred to as tissue-resident macrophages and belong to our innate immune system. Their primary job is to scavenge anything that does not belong to a healthy organ. However, they also produce a broad range of bioactive molecules and growth factors, ensuring that tissues are not only 'tidy' but grow, develop, and function.

"The special achievement of Elvira Mass is to have contributed to an important change in perspective when looking at the function of organs," writes the Scientific Council, chaired by Professor Thomas Boehm, Director at the Max Planck Institute for Immunobiology and Epigenetics in Freiburg, in substantiating its decision. “In order to understand how organs develop and what keeps them healthy, one no longer only looks at the bone marrow, but also at the yolk sac and thus at a completely different population of macrophages. This observation has important implications for medicine, because organ-specific defects might be associated with malfunctioning tissue-resident macrophages originally derived from the yolk sac".

Mass has provided evidence for the health-promoting function of resident macrophages in the mouse brain. Her attempt to manipulate microglia, as the brain-specific macrophages are called, were stimulated by the findings in patients suffering from a rare form of cancer called histiocytosis. This cancer arises from mutated macrophages, which multiply out of control. Many patients suffering from histiocytoses eventually develop neurodegenerative symptoms or behavioural deficits. Mass introduced the mutation typical for histiocytosis specifically into yolk sac-derived tissue-resident macrophages of mice and followed the development of the animals. She found that the mutated microglia cells no longer carried out their traditional tasks but instead attacked and eliminated neurons in their vicinity. Eventually, this led to paralysis demonstrating that mutated microglia can cause neurodegeneration in mice.

With funding recently awarded by the European Research Council, Mass will investigate which environmental factors change the epigenetic imprinting of the yolk sac-derived tissue-resident macrophages and how these changes affect the health of organs. To this end, she will, among other things, examine the influence of nanoplastics on macrophages. Particles that are smaller than 500 nanometers enter the embryo's blood via the placenta and could potentially damage the supporting function of the tissue-resident macrophages.

Short biography of Professor Dr. Elvira Mass
Elvira Mass (34) studied biology at the University of Bonn and did her Ph.D thesis at the Life and Medical Sciences Institute (LIMES) in Bonn. In 2014, she moved to Frederic Geissmann's laboratory at King's College in London and followed him a few months later to the Memorial Sloan-Kettering Cancer Center in New York. From there she returned to the LIMES Institute in 2017 as a group leader. In 2019, she became W2 Professor for "Integrated Immunology" at the University of Erlangen-Nuernberg. In 2020, she switched to a W2 / W3 professorship at the LIMES Institute. Mass has received several awards, including the Heinz Maier Leibnitz Prize in 2020, which is considered the most important award for young scientists in Germany.

Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers
The Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers, awarded for the first time in 2006, is conferred once a year by the Paul Ehrlich Foundation on a young investigator working in Germany for his or her outstanding achievements in the field of biomedical research. The prize money must be used for research purposes. University faculty members and leading scientists at German research institutions are eligible for nomination. The selection of the prizewinner is made by the Scientific Council on a proposal by the eight-person selection committee.

The Paul Ehrlich Foundation
The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president of the German Research Foundation, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Thomas Boehm, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.

Further information:
You can obtain selected publications, the list of publications and a photograph of the prizewinner from Dr. Hildegard Kaulen, phone: +49 (0) 6122/52718, e-mail: h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de.

Background on the award of the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers to Professor Elvira Mass, Ph.D (PDF)

For the first time, an international team of scientists from Goethe University and the University of Oklahoma has succeeded in filming quantum physical effects on a helium dimer as it breaks apart. The film shows the superposition of matter waves from two simultaneous events that occur with different probability: The survival and the disintegration of the helium dimer. This method might in future make it possible to track experimentally the formation and decay of quantum Efimov systems (Nature Physics, DOI 10.1038/s41567-020-01081-3).

FRANKFURT. Anyone entering the world of quantum physics must prepare themself for quite a few things unknown in the everyday world: Noble gases form compounds, atoms behave like particles and waves at the same time and events that in the macroscopic world exclude each other occur simultaneously.

In the world of quantum physics, Reinhard Dörner and his team are working with molecules which – in the sense of most textbooks – ought not to exist: Helium compounds with two atoms, known as helium dimers. Helium is called a noble gase precisely because it does not form any compounds. However, if the gas is cooled down to just 10 degrees above absolute zero (minus 273 °C) and then pumped through a small nozzle into a vacuum chamber, which makes it even colder, then – very rarely – such helium dimers form. These are unrivaledly the weakest bound stable molecules in the Universe, and the two atoms in the molecule are correspondingly extremely far apart from each other. While a chemical compound of two atoms commonly measures about 1 angstrom (0.1 nanometres), helium dimers on average measure 50 times as much, i.e. 52 angstrom.

The scientists in Frankfurt irradiated such helium dimers with an extremely powerful laser flash, which slightly twisted the bond between the two helium atoms. This was enough to make the two atoms fly apart. They then saw – for the very first time – the helium atom flying away as a wave and record it on film.

According to quantum physics, objects behave like a particle and a wave at the same time, something that is best known from light particles (photons), which on the one hand superimpose like waves where they can pile upor extinguish each other (interference), but on the other hand as “solar wind” can propel spacecraft via their solar sails, for example.

That the researchers were able to observe and film the helium atom flying away as a wave at all in their laser experiment was due to the fact that the helium atom only flew away with a certain probability: With 98 per cent probability it was still bound to its second helium partner, with 2 per cent probability it flew away. These two helium atom waves – Here it comes! Quantum physics! – superimpose and their interference could be measured.

The measurement of such “quantum waves” can be extended to quantum systems with several partners, such as the helium trimer composed of three helium atoms. The helium trimer is interesting because it can form what is referred to as an “exotic Efimov state”, says Maksim Kunitski, first author of the study: “Such three-particle systems were predicted by Russian theorist Vitaly Efimov in 1970 and first corroborated on caesium atoms. Five years ago, we discovered the Efimov state in the helium trimer. The laser pulse irradiation method we’ve now developed might allow us in future to observe the formation and decay of Efimov systems and thus better understand quantum physical systems that are difficult to access experimentally.”

Publication: Maksim Kunitski, Qingze Guan, Holger Maschkiwitz, Jörg Hahnenbruch, Sebastian Eckart, Stefan Zeller, Anton Kalinin, Markus Schöffler, Lothar Ph. H. Schmidt, Till Jahnke, Dörte Blume, Reinhard Dörner: Ultrafast manipulation of the weakly bound helium dimer. In: Nature Physics, https://doi.org/10.1038/s41567-020-01081-3

Pictures to download:

http://www.uni-frankfurt.de/95834340
Caption: Dr Maksim Kunitski next to the COLTRIMS reaction microscope at Goethe University, which was used to observe the “quantum wave”. (Photo: Uwe Dettmar for Goethe University)

http://www.uni-frankfurt.de/95834284
Caption: Professor Reinhard Dörner (left) and Dr Maksim Kunitzki in front of the COLTRIMS reaction microscope at Goethe University, which was used to observe the quantum wave. (Photo: Goethe University Frankfurt)

Video: https://static-content.springer.com/esm/art%3A10.1038%2Fs41567-020-01081-3/MediaObjects/41567_2020_1081_MOESM2_ESM.mp4

Further information
Professor Reinhard Dörner
Institute for Nuclear Physics
Tel.: +49 (0)69 798-47003
doerner@atom.uni-frankfurt.de
https://www.atom.uni-frankfurt.de/