Press releases

FRANKFURT. About ten percent of Parkinson's cases can be ascribed to mutations in the LRRK2 gene. Five research teams from the University of California in San Diego, Goethe University Frankfurt and the University of Konstanz want to explain in the next few years how mutations in the LRRK2 gene trigger Parkinson's disease and what possible targets there are for drugs. The US-American initiative “Aligning Science Across Parkinson's" has made the equivalent of € 6.1 million available for this project.

In the early 2000s, it was discovered that in many Parkinson's patients a certain enzyme called LRRK2 mutates and evidently plays a significant role in five to ten percent of hereditary Morbus Parkinson and between one and five percent of the spontaneous form. LRRK2 is an enzyme that attaches phosphate groups to other proteins in the human cell and is far more active than normal in the brain cells of Parkinson's patients, leading it to block transport processes in the cell. Many inhibitors against the LRRK2 enzyme have already been tested in the past, but they are not sufficiently effective or their side-effects are too severe.

The five teams from USA and Germany want now to elucidate in detail the enzyme's structure and how it works in the cell and thus create a basis for the targeted production of inhibitors. A first three-dimensional structure of the LRRK2 protein was recently published by the research team in the journal Nature. The initiative “Aligning Science Across Parkinson's", which is backed by The Michael J. Fox Foundation for Parkinson's Research, is supporting the project financially.

Co-Project Manager Stefan Knapp, Professor for Pharmaceutical Chemistry at Goethe University, explains: “By comparing LRRK2 mutations in Parkinson's patients with normal LRRK2, we want to find out which tasks LRRK2 assumes in the cell, how the enzyme moves three-dimensionally, and how the mutated LRRK2 contributes to nerve cells dying off. While the expertise of our colleagues in the USA lies in various imaging methods, here in Frankfurt we'll develop chemical probes to localize and study LRRK2 in cells and we will produce recombinant LRRK2 variants that will help us to understand their three-dimensional structure."

Co-Project Manager Florian Stengel, Professor for Cellular Proteostasis at the University of Konstanz, says: “In the framework of this project, we here in Konstanz want to identify the cellular interaction partners of LRRK2. In this way, we'll be able to complete our picture of its cellular role and thus make it possible to develop a drug against LRRK2 mutated Morbus Parkinson."

Article on the first three-dimensional structure of the LKKR2 protein: C K Deniston, J Salogiannis, S Mathea, D M Snead, I Lahiri, M Matyszewski, O Donosa, R Watanabe, J Böhning, A K Shiau, S Knapp, E Villa, S L Reck-Peterson, A E Leschziner. Structure of LRRK2 in Parkinson's disease and model for microtubule interaction. Nature. 2020 Aug 19 https://pubmed.ncbi.nlm.nih.gov/32814344/

Pictures to download: www.uni-frankfurt.de/92946466

Caption: Professor Stefan Knapp, Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt (Foto: Uwe Dettmar)

Further information:
Professor Stefan Knapp
Institute of Pharmaceutical Chemistry
Goethe University Frankfurt
Phone: +49 69 798-29871
knapp@pharmchem.uni-frankfurt.de

Professor Florian Stengel
Department of Biology / Laboratory of Cellular Proteostasis and Mass Spectrometry
University of Konstanz
Phone: +49 7531 88-5172
florian.stengel@uni-konstanz.de

FRANKFURT. Atmospheric researchers from Goethe University have demonstrated that air purifiers with a class H13 filter (HEPA) can lower aerosol concentration in a classroom by 90 percent within 30 minutes. Because this significantly reduces the risk of airborne infection with SARS-CoV-2, the scientists recommend placing such air purifiers in classrooms. In most cases, students and teachers did not find the noise made by the purifier disturbing. The study is now available as a preprint, prior to appearing in a scientific journal. (https://doi.org/10.1101/2020.10.02.20205633)

The most dangerous route to an infection with SARS-CoV-2 is via the air: For example, when infected persons sneeze or cough, they catapult relatively large droplets which, however, sink to the ground within a radius of two metres. Important are also aerosols, much smaller droplets, which we emit when speaking or breathing. Studies show that infectious SARS-CoV-2 pathogens can still be detected in such aerosols over three hours after emission and several metres away from an infected person. The fluid in such aerosol particles evaporates quickly, making them smaller and able to disperse in a room within a few minutes.

Together with his team, Joachim Curtius, Professor for Experimental Atmospheric Research at Goethe University, tested four air purifiers in a classroom with 27 students and their teachers over a period of a week. The purifiers had a simple prefilter for coarse dust particles and fluff as well as HEPA and active carbon filters. Together, the filters processed between 760 and 1,460 m3 of air per hour. Apart from aerosol load, the researchers also measured the volume of fine dust particles and CO2 concentration and analysed the noise levels caused by the device. The result: Half an hour after switching it on, the air purifiers had removed 90 percent of the aerosols from the air.

Professor Curtius explains: “On the basis of our measurement data, we've calculated a model that allows the following estimate: An air purifier lowers the amount of aerosols to such a considerable degree that the risk of being infected by a highly contagious person, a superspreader, is greatly reduced. That's why we're recommending that schools use HEPA air purifiers this winter with a sufficiently high air flow rate."

Noise measurements and a survey among students and teachers revealed that in most cases the noise made by the air purifier was not considered disturbing, provided that the appliance was not running at the highest level.

The researchers also measured that the air purifier – apart from lowering the risk of infection –additionally reduced allergens and fine dust particles (PM10). Joachim Curtius: “An air filter does not, however, replace opening the window at regular intervals, which is important for decreasing CO2 concentration in the room. Our measurements in the classrooms showed that levels often exceeded the recommended limits. Here, we recommend installing CO2 sensors so that students and teachers can monitor this themselves."


Publication: Joachim Curtius, Manuel Granzin, Jann Schrod: Testing mobile air purifiers in a school classroom: Reducing the airborne transmission risk for SARS‐CoV‐2. Preprint: medRxiv 2020.10.02.20205633; doi: https://doi.org/10.1101/2020.10.02.20205633

Further information:
Professor Dr. Joachim Curtius
Institute for Atmospheric and Environmental Sciences
Goethe University
Tel.: +49 69 798-40258
curtius@iau.uni-frankfurt.de

FRANKFURT. Geoscientists from Goethe University have found the largest extraterrestrial diamonds ever discovered – a few tenths of a millimetre in size nevertheless – inside meteorites. Together with an international team of researchers, they have now been able to prove that these diamonds formed in the early period of our solar system when minor planets collided together or with large asteroids. These new data disprove the theory that they originated deep inside planets – similar to diamonds formed on Earth - at least the size of Mercury. (PNAS, https://www.pnas.org/content/early/2020/09/22/1919067117)

It is estimated that over 10 million asteroids are circling the Earth in the asteroid belt. They are relics from the early days of our solar system, when our planets formed out of a large cloud of gas and dust rotating around the sun. When asteroids are cast out of orbit, they sometimes plummet towards Earth as meteoroids. If they are big enough, they do not burn up completely when entering the atmosphere and can be found as meteorites. The geoscientific study of such meteorites makes it possible to draw conclusions not only about the evolution and development of planets in the solar system but also their extinction.

A special type of meteorites are ureilites. These are fragments of a larger celestial body – probably a minor planet – which was smashed to pieces through violent collisions with other minor planets or large asteroids. Ureilites often contain large quantities of carbon, among others in the form of graphite or nanodiamonds. The diamonds on the scale of over 0.1 and more millimetres now discovered cannot have formed when the meteoroids hit the Earth. Impact events with such vast energies would make the meteoroids evaporate completely. That is why it was so far assumed that these larger diamonds – similar to those in the Earth's interior – must have been formed by continuous pressure in the interior of planetary precursors the size of Mars or Mercury.  

Together with scientists from Italy, the USA, Russia, Saudi Arabia, Switzerland and the Sudan, researchers from Goethe University have now found the largest diamonds ever discovered in ureilites from Morocco and the Sudan and analysed them in detail. Apart from the diamonds of up to several 100 micrometres in size, numerous nests of diamonds on just nanometre scale as well as nanographite were found in the ureilites. Closer analyses showed that what are known as londsdalite layers exist in the nanodiamonds, a modification of diamonds that only occurs through sudden, very high pressure. Moreover, other minerals (silicates) in the ureilite rocks under examination displayed typical signs of shock pressure. In the end, it was the presence of these larger diamonds together with nanodiamonds and nanographite that led to the breakthrough.

Professor Frank Brenker from the Department of Geosciences at Goethe University explains:
“Our extensive new studies show that these unusual extraterrestrial diamonds formed through the immense shock pressure that occurred when a large asteroid or even minor planet smashed into the surface of the ureilite parent body. It's by all means possible that it was precisely this enormous impact that ultimately led to the complete destruction of the minor planet. This means – contrary to prior assumptions – that the larger ureilite diamonds are not a sign that protoplanets the size of Mars or Mercury existed in the early period of our solar system, but nonetheless of the immense, destructive forces that prevailed at that time."


The international research team comprises scientists from the following institutions:

Department of Geosciences, University of Padova, Italy
Department of Geosciences, Goethe University, Frankfurt, Germany
Lunar and Planetary Institute, USRA, Houston, Texas, USA
Department of Earth and Environmental Sciences, University of Pavia, Italy
Astromaterials Research and Exploration Science Division, Jacobs JETS, Johnson Space Center, NASA, Houston, Texas, USA
CNR Institute of Geosciences and Earth Resources, Padua, Italy
Vereshchagin Institute for High Pressure Physics RAS, Troitsk, Moscow, Russia
NASA Astromaterials Acquisition and Curation Office, Johnson Space Center, NASA, Houston, Texas, USA
Department of Civil, Environmental and Mechanical Engineering, University of Trento, Italy
Saudi Aramco R&D Center, Dhahran, Saudi Arabia
Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland
SETI Institute, Mountain View, California, USA
Department of Physics and Astronomy, University of Khartoum, Khartoum, Sudan


Publication: Fabrizio Nestola, Cyrena A. Goodrich, Marta Morana, Anna Barbaro, Ryan S. Jakubek, Oliver Christ, Frank E. Brenker, Maria C. Domeneghetti, Maria C. Dalconi, Matteo Alvaro, Anna M. Fioretti, Konstantin Litasov, Marc D. Fries, Matteo Leoni, Nicola P. M. Casati, Peter Jenniskens, Muawia H. Shaddad: Impact shock origin of diamonds in ureilite meteorites. Proceedings of the National Academy of Science https://www.pnas.org/content/early/2020/09/22/1919067117

Images to download:
Picture1: Planetary collision
Caption: Artist's impression of the collision of two protoplanets. Credits: NASA/SOFIA/Lynette Cook
https://www.nasa.gov/image-feature/what-happens-when-planets-collide

Picture2: Rock sample from ureilite minor planet
Caption: Photo of a rock sample from the ureilite minor planet, found as a meteorite in the Sahara. Length of the fragments about 2cm. Credits: Oliver Christ https://www.muk.uni-frankfurt.de/92537913

Picture3: Colour coded Raman spectroscopic map of the ureilite studied. diamond (red), graphite (blue). Credits: Cyrena Goodrich http://www.uni-frankfurt.de/92538164


Further information:
Professor Frank E. Brenker
Department of Geosciences / NanoGeoscience
Goethe University
Tel: +49 69 798 40134
f.brenker@em.uni-frankfurt.de

FRANKFURT. Researchers at Goethe University Frankfurt and the university of Würzburg have developed a new compound for treating cancer. It destroys a protein that triggers its development.

The villain in this drama has a pretty name: Aurora – Latin for dawn. In the world of biochemistry, however, Aurora (more precisely: Aurora-A kinase) stands for a protein that causes extensive damage. There, it has been known for a long time that Aurora often causes cancer. It triggers the development of leukemias and many pediatric cancers, such as neuroblastomas.

Researchers at the universities of Frankfurt and Würzburg have now developed a drug that can disarm Aurora. Stefan Knapp, Professor of Pharmaceutical Chemistry at Goethe University Frankfurt, and Dr. Elmar Wolf, biochemist and research group leader at the Biocenter of Julius-Maximilians-Universität Würzburg (JMU), have played a leading role in this development. The results of their work have now been published in the latest issue of Nature Chemical Biology.

Making tumor-promoting proteins disappear

Cancers are usually triggered by tumorigenic proteins. Because cancer cells produce more of these proteins than normal cells, the dynamics are additionally increased. A common therapeutic approach is therefore to inhibit the function of these proteins with drugs. Although the proteins are then still there, they no longer function as well. This makes it possible to combat the tumor cells.
 
However, the development of these inhibitors is difficult and has so far not been successful for all tumor-promoting proteins. To date, none of the candidates that inhibit Aurora has shown the desired results in clinical practice. The dream of many scientists is therefore to develop a drug that not only inhibits the tumor-promoting proteins but makes them disappear completely. A promising approach along this path could be a new class of substances with the scientific name “PROTAC".

In vitro cancer cells die

“We have developed such a PROTAC for Aurora," says Elmar Wolf. This PROTAC completely degrades the Aurora protein in cancer cells. Such cells cultivated in the laboratory died as a result. Wolf describes the mode of action of this substance as follows: “The tumor needs certain tumor-promoting proteins, which we can imagine as the pages of a book. Our PROTAC substance tears out the 'Aurora' pages and destroys them with the help of the machinery that every cell has to degrade old and broken proteins." PROTAC thus “shreds" the Aurora protein, as it were, until nothing of it remains.

Professor Stefan Knapp from the Institute of Pharmaceutical Chemistry at Goethe University explains: “Aurora-A kinase is present in much higher concentrations in many cancer tissues than in healthy tissue and it also plays a key role in prostate cancer. Blocking the activity of Aurora-A kinase alone seems not a promising approach as none of the many clinically tested drug candidates has achieved clinical approval. With our PROTAC variant, we inhibit Aurora-A kinase via another, possibly more effective mechanism, which may open up new treatment options. That's why in the next step we'll test effectiveness and tolerance in animal models."


Publication: PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase. Bikash Adhikari, Jelena Bozilovic, Mathias Diebold, Jessica Denise Schwarz, Julia Hofstetter, Martin Schröder, Marek Wanior, Ashwin Narain, Markus Vogt, Nevenka Dudvarski Stankovic, Apoorva Baluapuri, Lars Schönemann, Lorenz Eing, Pranjali Bhandare, Bernhard Kuster, Andreas Schlosser, Stephanie Heinzlmeir, Christoph Sotriffer, Stefan Knapp and Elmar Wolf. Nature Chemical Biology, 28.09.2020. https://www.nature.com/articles/s41589-020-00652-y

PROTACS: The cluster project PROXIDRUGS at Goethe University Frankfurt focuses on PROTACS (Proteolysis Targeting Chimeric Molecules): https://aktuelles.uni-frankfurt.de/englisch/proxidrugs-project-led-by-goethe-university-included-in-clusters4future-programme/

Further Information:
Prof. Dr. Stefan Knapp
Institut of Pharmaceutical Chemistry
Goethe University Frankfurt
Phone: +49 69 798 29871
knapp@pharmchem.uni-frankfurt.de

FRANKFURT. Walter Benjamin's collection of children's books is to be saved for posterity. The national government, the Federal State of Hesse and the Department for Children's and Young Adult Literature Research have joined forces to finance the first restoration work on this valuable historical archive.

The collection previously owned by Walter Benjamin comprises just 204 books. Yet it is particularly valuable in several respects: For research, it delivers important insights into this great intellectual mind, who was a close friend of Theodor W. Adorno and belonged to the circle of the Frankfurt School. Some of the books stem from Benjamin's own childhood, and in his writings and radio broadcasts he also dealt with children's literature based on his collection. Moreover, the collection is composed entirely of beautiful and rare copies: Benjamin, who was born in Berlin, primarily built up his collection according to aesthetic criteria; he was especially interested in illustrated and artistically ornate children's books.

Having been purchased from Benjamin's heirs, the collection came to the Department for Children's and Young Adult Literature Research in the 1980s. It was the explicit wish of Stefan Benjamin, Walter Benjamin's son, that the collection return to Germany. It was displayed at an exhibition at the University Library and an elaborate catalogue was produced (available for download from the department's website: www.uni-frankfurt.de/65668457/Die_Kinderbuchsammlung_Walter_Benjamin_Katalog.pdf).

Since then, the books have been kept in a steel cabinet in the department's library. To be able to continue making them accessible for research, restoration work is urgently required: The books are used a great deal and partially damaged as a result, the ravages of time have done the rest. They will now first be “stabilised". Part of the collection has already been sent to the Centre for Book Conservation in Leipzig, where first of all the paper will be deacidified, the cover and edges stabilised, and customised boxes with hinged lids made for each individual book.

“With modest means, Benjamin assembled the books from his own childhood into a collection," explains Dr Felix Giesa, custodian at the Department for Children's and Young Adult Literature Research. He primarily collected books according to aesthetic criteria, he adds, mostly illustrated works from the 19th century. Apart from various editions of Grimms' Children's and Household Tales, fairytales by Wilhelm Hauff and Charles Perrault are also part of the collection. In addition, what are known as transformation picture books, such as a rare book by Christian Gottfried Heinrich Geissler dated 1815, make up an important part of the valuable collection.

With funds from the government's Coordination Office for the Preservation of Written Cultural Heritage, which will assume 50 percent of the costs, from the Federal State of Hesse, which will bear 40 percent via the Hessian Ministry of Higher Education, Research, Science and the Arts, and from the budget of Professor Ute Dettmar, the collection will first be stabilised and catalogued, after which an exhibition and a symposium are planned. A total of around € 30,000 is available for these measures. Later, the collection will also be digitised so that it is available for Benjamin research in Germany and abroad – without its use leaving further traces in the originals.


Images can be downloaded under the following link: http://www.uni-frankfurt.de/92258379

Caption: Much-used and correspondingly worse for wear: Walter Benjamin's collection of children's books is to be saved for posterity. Funds for this are now available. (Photo: Uwe Dettmar)