Press releases – November 2023

Leukemia is the most common type of cancer in children. Treatment involves intensive chemotherapy, which has severe side effects due to its non-specific mode of action. A team from the Department of Pediatrics and the Institute for Experimental Pediatric Hematology and Oncology at Goethe University Frankfurt has now discovered a site in the DNA of cancer cells that is essential for leukemia cells to survive. Cancer cells in which the gene encoded at this site was modified experimentally died off. The gene locus thus constitutes a promising target for an alternative therapy in the future. 

The term 'leukemia' encompasses various forms of blood cancer, including acute myeloid leukemia (AML). In AML, blood cells in the early stages – the stem cells and the precursor cells that develop out of them – degenerate. AML is the second most common leukemia in children, accounting for around four percent of all malignant diseases in childhood and adolescence. Despite intensive chemotherapy, only around half of those affected survive without relapsing. About one third of children are dependent on a stem cell donation. Since non-specific chemotherapies have severe side effects, there is an urgent need to find new and specific therapy approaches. 

A team led by Jan-Henning Klusmann from the Department of Pediatrics and Dirk Heckl from the Institute for Experimental Pediatric Hematology and Oncology at Goethe University Frankfurt has now discovered an unusual “Achilles heel" in AML cells. For their study, which has now been published, they looked at a specific group of nucleic acids in leukemia cells: noncoding RNAs. Just like regular messenger RNAs (mRNAs), these are produced through gene transcription. However, unlike mRNAs, noncoding RNAs are not translated into proteins but instead often assume regulatory functions, for example in cell growth and cell division. A typical characteristic of cancer cells is a massive disruption of regulatory processes. This makes noncoding RNAs an interesting starting point in the fight against cancer. 

Against this background, the researchers led by Klusmann and Heckl wanted to know more about the role of noncoding RNAs in AML cells. For this purpose, they compiled a kind of inventory of these molecules in cancer cells taken from sick children and compared the resulting pattern with that of healthy blood stem cells. AML cells differentially expressed almost 500 noncoding RNAs in comparison to healthy cells – an indication that they could perform an important function in cancer cells. To validate this, the researchers turned off every single one of these RNA molecules by preventing the coding gene in the genome from being read. The most distinct effect they found was for the gene MYNRL15: Cancer cells in which this gene was turned off lost their ability to replicate indefinitely and died off. 

Surprisingly, however, it was not the absence of noncoding RNAs that was responsible for this effect, as Klusmann comments: “The regulatory function we observed is due to the MYNRL15 gene itself." The team was able to show that destroying the gene altered the spatial organization of the chromatin, i.e. the three-dimensional structure of the genome. “This led to the deactivation of genes that AML cells need for survival," says Klusmann. This offers a new and unforeseen possibility for fighting leukemia. 

What is significant against this background is the fact that the inhibitory effect triggered by the modified MYNRL15 gene could be observed in different AML cell lines. These cells originated both from children as well as adults and included various subtypes of the disease – among them one common in people with Down syndrome. “The fact that all the leukemias we studied were dependent on this gene locus tells us it must be important," concludes Klusmann. The researchers now hope that the cancer cells' dependence on MYNRL15 can be used to develop a specific gene therapy. “In our study, we systematically examined noncoding RNAs and their genes in AML cells for the first time, and in the process we identified a gene locus that constitutes a promising target for developing a therapy in the future," says Klusmann, summing up. 

Publication: Michelle Ng, Lonneke Verboon, Hasan Issa, Raj Bhayadia, Marit Willemijn Vermunt, Robert Winkler, Leah Schüler, Oriol Alejo, Konstantin Schuschel, Eniko Regenyi, Dorit Borchert, Michael Heuser, Dirk Reinhardt, Marie-Laure Yaspo, Dirk Heckl, Jan-Henning Klusmann: Myeloid leukemia vulnerabilities embedded in long noncoding RNA locus MYNRL15. iScience 26, 107844 (2023) https://doi.org/10.1016/j.isci.2023.107844 

Further Information:
Professor Jan-Henning Klusmann
Director
Department of Pediatrics
University Hospital Frankfurt
Tel.: +49 69 6301-5094
kkjm.direktor@gmail.com
www.leukemia-research.de 

Professor Dirk Heckl
Institute for Experimental Pediatric Hematology and Oncology
Goethe University Frankfurt
d.heckl@kinderkrebsstiftung-frankfurt.de

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: +49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de

After a five-year break, the large LHC accelerator at the CERN international research institute has once again brought lead ions to collision. During the process, the colliding matter dissolves into its components for an extremely short time, reaching a state like the one that prevailed in the universe a few millionths of a second after the Big Bang. The particle tracks of these collisions are recorded by the house-sized ALICE detector, which Goethe University researchers helped upgrade. Already during the first month of the new data collection period, a new record was set: 20 times more collision events were registered than in the data-taking periods of previous years combined. 

On September 26, 2023, the accelerator team at the CERN European Council for Nuclear Research in Geneva declared stable lead-beam conditions, ushering in the first data-taking campaign of lead-ion collisions in five years. From then until the late evening of October 29, the accelerator produced lead-ion collisions at the world's highest-ever collision energy of 5.36 terra electron volts per colliding nuclear particle (nucleon-nucleon collision). In addition to the collision energy, the collision rates also increased significantly compared to the data taking periods of previous years. The ALICE detector, specialized in recording lead atomic nucleus collisions, recorded 20 times more events than in the previous four data-taking periods combined – each of which lasted about one month, and the first of which dates back to 2010. 

This is important because of the tremendous number of particles that are created and decay in a very short timeframe during the collisions. Recording the tracks of these particles allows conclusions to be drawn about exactly what happens at the moment of collision and shortly thereafter: The particles dissolve into their elementary components – quarks and gluons – and form a kind of "matter soup", a so-called quark-gluon plasma. Immediately afterwards, new, very unstable particles form again, which finally transform into stable particles in complex decay chains. In this way, researchers in the ALICE experiment are studying the properties of matter as it existed shortly after the Big Bang. 

Research groups from Goethe University Frankfurt are part of the experiments: The new record was first made possible because the world's most powerful particle accelerator, the Large Hadron Collider (LHC), was upgraded during the four-year reconstruction phase from 2018 to 2022. The upgrades of the ALICE detector during the same timeframe enable it to record the traces of the LHC's higher collision rates. 

To carry out these upgrades, it was necessary to replace the readout detectors of the experiment's central detector, the so-called Time Projection Chamber (TPC). Professor Harald Appelshäuser from Goethe University's Institute for Nuclear Physics Frankfurt (IKF) serves as project lead for this 10-year undertaking. 

The enormous amount of data generated during the measurements – which reaches the range of terabytes per second for the TPC alone – constitutes a major challenge. To be able to sufficiently reduce the amount of data stored, this data stream must be processed in real time, using effective pattern recognition methods. The Event Processing Nodes (EPN) computing cluster was set up specifically for this experiment. Based on both conventional computing cores (CPUs) and special graphics processors, the EPN project is led by Volker Lindenstruth, Professor for High-Performance Computer Architecture at Goethe University and Fellow at the Frankfurt Institute for Advanced Studies (FIAS). 

The measurements at higher collision rates are a major success for CERN's heavy ion program. Prof. Appelshäuser: "It's finally happening! We have been working towards this for 10 years, and are looking forward to evaluating the data we have now obtained. I would especially like to thank Germany's Federal Ministry of Education and Research for its long-term funding, not least since the only way for research projects of this dimension to be successful is by having such a reliable partner on board." 

Background:
News release: ALICE experiment at CERN starts test operation with lead ions (2022)
https://aktuelles.uni-frankfurt.de/english/big-bang-research-alice-experiment-at-cern-starts-test-operation-with-lead-ions/?highlight=ALICE
About the ALICE experiment:
https://home.cern/science/experiments/alice 

Picture download:
https://www.uni-frankfurt.de/129304631 

Caption:
To carry out the upgrade, the ALICE detector had to be opened. Photo: Sebastian Scheid, Goethe University Frankfurt 

Further Information:
Professor Harald Appelshäuser
Institute for Nuclear Physics
Goethe University Frankfurt
Tel: +49 (0) 69 798-47034 or 47023
appels@ikf.uni-frankfurt.de
@ALICExperiment @goetheuni

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: +49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de

An AI model developed by a team of scientists from Goethe University Frankfurt and the University of Birmingham, led by Niamh Eastwood and Prof. Luisa Orsini, shows how water pollution, extreme weather events and rising temperatures can change and irreversibly damage the ecosystem of a freshwater lake over many decades. The model uses weather and climate data as well as data extracted from a sediment core taken from the lake and could in future be used to predict how ecosystems react to complex environmental changes. As such, it could serve as a "time machine for biodiversity", so to speak, explaining past processes while simultaneously pointing to future ecological dangers. 

The sediments of lakes and rivers are the long-term memory of bodies of water: It is here where, layer by layer, mineral, organic and chemical particles and substances are deposited over time. Using a sediment core from the "Ring Lake", located near the city of Braedstrup in Denmark, the team of German and British scientists analyzed the DNA residues of plants, animals and bacteria as well as environmental toxins like pesticides or herbicides that have entered the lake over time and been deposited in the sediments. This allowed them to reconstruct the changes that have taken place in the lake's ecological community as well as the pollution caused by nitrates and biocides, for instance, over the past 100 years. 

"The subject of our investigation, the 'Ring Lake' in Denmark, is a body of water that was hardly polluted at the beginning of the 20th century. Over the course of the century, however, the lake was exposed to considerable environmental pollution. In the last years of the 20th century, water quality improved significantly," explains Prof. Henner Hollert, environmental toxicologist at Goethe University Frankfurt, Fraunhofer IME and the LOEWE Center TBG for Translational Biodiversity Genomics. Coupled with its undisturbed sediment stratification, which makes the years visible in a manner similar to that of annual rings of a tree trunk, this made the lake such an interesting research subject. 

The scientific team proceeded to link the analysis data from the drill core with climate records, focusing in particular on extreme temperatures and precipitation levels. Using artificial intelligence, they developed a model that explains the influence of environmental changes on the composition of the freshwater community and resolves them in terms of time and space. Their finding: 90 percent of the changes in the functional biodiversity of Ring Lake were due to the introduction of insecticides and fungicides in conjunction with extreme temperature and precipitation events. 

Although nearby agricultural activity decreased at the end of the century, leading to an improvement in water quality, the German-British team of scientists found that this did not restore the lake's original ecological condition. 

Henner Hollert: "We were able to show that the loss of biodiversity in an ecosystem is not completely reversible: Biocenosis no longer functions as it did before, since species that performed certain services within the ecosystem are missing. We will now test our AI system – which we refer to as our 'time machine for biodiversity' – on other lakes, including as part of an ongoing interdisciplinary German Research Foundation (DFG) project on the interaction between humans and the environment in the late Middle Ages. Our partners in the latter are the Technical University of Darmstadt, Helmholtz Centre Potsdam – GFZ German Research Centre for Geosciences, the State Service for Heritage Protection and Management Baden-Wuerttemberg, and the Universities of Tübingen and Braunschweig. Lessons from the past can help us for the future: We aim to provide authorities with a warning system that can assess ecologically threatening developments at an early stage, thereby allowing countermeasures to be taken, for example restricting the use of certain biocides in the vicinity of an ecotope." 

Ecotoxicologist Professor Luisa Orsini, who also holds a Hückmann Endowed Visiting Professorship at Goethe University Frankfurt and is a member of the RobustNature network of excellence, underlines the advantages of the new AI-based method: "The high-throughput analyses we use allow us to observe the entirety of living organisms in an ecosystem and relate them to their environment. With this in hand, we can assess the long-term trends in an ecosystem's development much better than with previous monitoring methods, which only focus on one or a few species, and identify the factors with the greatest impact on biodiversity." 

Publication: Niamh Eastwood, Jiarui Zhou, Romain Derelle, Mohamed Abou-Elwafa Abdallah, William A Stubbings, Yunlu Jia, Sarah E Crawford, Thomas A Davidson, John K Colbourne, Simon Creer, Holly Bik, Henner Hollert, Luisa Orsini: 100 years of anthropogenic impact causes changes in freshwater functional biodiversity. eLife (2023) https://elifesciences.org/articles/86576 

About the research cluster RobustNature: https://www.robustnature.de/en/ 

Further Information:
Professor Henner Hollert
Institute for Ecology, Evolution und Diversity
Goethe University Frankfurt
and Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Schmallenberg, and LOEWE-Center for Translational Biodiversity Genomics (LOEWE‐TBG),Frankfurt
Tel: +49 (0)69 798-42171
hollert@bio.uni-frankfurt.de
https://www.bio.uni-frankfurt.de/43970666/Abt__Hollert

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: +49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de

Goethe University Frankfurt and the Hebrew University of Jerusalem (HUJI) today announced another significant addition to their existing scientific cooperation in the field of childhood research: The two universities signed a cooperation agreement to establish the Center for Childhood and Child Welfare in Context. 

The collaboration builds on a long-standing partnership characterized by extensive research, support for early career researchers and excellence in university teaching. Notable joint initiatives include an international study on the well-being of children, other empirical studies on the rights, interests and needs of children and adolescents, as well as research on violence and neglect in families or educational institutions in both Germany and Israel. The two universities have also been holding an annual German-Israeli Master's seminar since 2016. 

The main aim of this latest research cooperation is to deepen and expand academic and scientific cooperation in both childhood as well as social science research. The new Center for Childhood and Child Welfare will focus on a number of topics, including the implementation of children's rights, dealing with structural bottlenecks such as a shortage of skilled workers, and experiences with displacement, among others. In addition, the center will also research issues related to professionalization, quality, digitality, digitalization, global warming and biodiversity. Another one of its aims is to help ensure children and adolescents have a voice in research, and to examine age as a social category. 

Scientists from a wide array of different disciplines – such as childhood and family research, educational science, pedagogy, migration research, social work and healthcare – from both universities will be involved in the center, which sets out to deliver an innovative contribution to global childhood research and promote networking in this field. 

Goethe University President Prof. Enrico Schleiff: "I am delighted to see our two universities pool their respective strengths and potential even more in the field of childhood research, which is so important to our society. The Center for Childhood and Child Welfare in Context further intensifies and expands our existing close cooperation. I would like to thank everyone involved at both universities, first and foremost among them Prof. Asher Ben-Arieh and Prof. Sabine Andresen, for their great commitment to making this future-oriented international cooperation possible." 

Prof. Sabine Andresen, Professor of Educational Science at Goethe University Frankfurt, with a focus on social pedagogy and family research: "Our experiences with the master's seminars especially, in which students from Frankfurt and Jerusalem not only learn together, but also discuss and compare what it was like to grow up in both countries, have led us to deepen the cooperation. For students who will later work in youth welfare offices or as child protection specialists for example, this exchange about both systems, about tailor-made services or barriers to the protection of children and adolescents is game-changing. We also found that a lot of friendships have emerged from these seminars." 

Prof. Asher Ben-Arieh, Dean of HUJI's School of Social Work and Social Welfare, underscores the importance of this latest collaboration: "This cooperation between the Hebrew University of Jerusalem and Goethe University Frankfurt is proof of our joint commitment to advancing research in the field of childhood studies. By joining forces, we aim to create a better and safer future for children worldwide. Through our combined expertise and dedication, we can better understand and improve the lives of children and families." 

Contact: Prof. Sabine Andresen, Professor for Educational Science with a focus on social pedagogy and family research, Institute for Social Pedagogy and Adult Education, Faculty of Educational Sciences, Goethe University Frankfurt. S.Andresen@em.uni-frankfurt.de

Editor: Dr. Dirk Frank, Press Officer / Deputy Head of PR and Communication, Goethe University Frankfurt, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Phone +49 (0)69 798–13753, frank@pvw.uni-frankfurt.de