Goethe-Universit盲t 鈥� Press releases

51猎奇 PR & Communication Department聽

Jul 20 2021

15:26

Researchers at 51猎奇 find small molecules as binding partners for genomic RNA of the coronavirus

SARS-CoV-2: Achilles鈥� heel of viral RNA

Certain regions of the SARS-CoV-2 genome might be a suitable target for future drugs. This is what researchers at Goethe University, together with their collaborators in the international COVID-19-NMR consortium, have now discovered. With the help of dedicated substance libraries, they have identified several small molecules that bind to certain areas of the SARS-CoV-2 genome that are almost never altered by mutations.

FRANKFURT. When SARS-CoV-2 infects a cell, it introduces its RNA into it and re-programmes it in such a way that the cell first produces viral proteins and then whole viral particles. In the search for active substances against SARS-CoV-2, researchers have so far mostly concentrated on the viral proteins and on blocking them, since this promises to prevent, or at least slow down, replication. But attacking the viral genome, a long RNA molecule, might also stop or slow down viral replication.

The scientists in the COVID-19-NMR consortium, which is coordinated by Professor Harald Schwalbe from the Institute of Organic Chemistry and Chemical Biology at 51猎奇, have now completed an important first step in the development of such a new class of SARS-CoV-2 drugs. They have identified 15 short segments of the SARS-CoV-2 genome that are very similar in various coronaviruses and are known to perform essential regulatory functions. In the course of 2020 too, these segments were very rarely affected by mutations.

The researchers let a substance library of 768 small, chemically simple molecules interact with the 15 RNA segments and analysed the result by means of NMR spectroscopy. In NMR spectroscopy, molecules are first labelled with special types of atoms (stable isotopes) and then exposed to a strong magnetic field. The atomic nuclei are excited by means of a short radio frequency pulse and emit a frequency spectrum, with the help of which it is possible to determine the RNA and protein structure and how and where small molecules bind.

This enabled the research team led by Professor Schwalbe to identify 69 small molecules that bound to 13 of the 15 RNA segments. Professor Harald Schwalbe: 鈥淭hree of the molecules even bind specifically to just one RNA segment. Through this, we were able to show that the SARS-CoV-2 RNA is highly suitable as a potential target structure for drugs. In view of the large number of SARS-CoV-2 mutations, such conservative RNA segments, like the ones we've identified, are particularly interesting for developing potential inhibitors. And since the viral RNA accounts for up to two thirds of all RNA in an infected cell, we should be able to disrupt viral replication on a considerable scale by using suitable molecules." Against this background, Schwalbe continues, the researchers have now already started follow-up trials with readily available substances that are chemically similar to the binding partners from the substance library.

Publication: Sridhar Sreeramulu, Christian Richter, Hannes Berg, Maria A Wirtz Martin, Bet眉l Ceylan, Tobias Matzel, Jennifer Adam, Nadide Altincekic, Kamal Azzaoui, Jasleen Kaur Bains, Marcel J.J. Blommers, Jan Ferner, Boris F眉rtig, M. G枚bel, J Tassilo Gr眉n, Martin Hengesbach, Katharina F. Hohmann, Daniel Hymon, Bozana Knezic, Jason Martins, Klara R Mertinkus, Anna Niesteruk, Stephen A Peter, Dennis J Pyper, Nusrat S. Qureshi, Ute Scheffer, Andreas Schlundt, Robbin Schnieders, Elke Stirnal, Alexey Sudakov, Alix Tr枚ster, Jennifer V枚gele, Anna Wacker, Julia E Weigand, Julia Wirmer-Bartoschek, Jens W枚hnert, Harald Schwalbe: Exploring the druggability of conserved RNA regulatory elements in the SARS-CoV-2 genome, Angewandte Chemie International Edition,

About the COVID-19-NMR consortium
Worldwide, over 40 working groups from 18 countries with a total of 230 scientists are conducting research within the COVID-19-NMR consortium. In Frankfurt, 45 doctoral and post-doctoral candidates have partly been working in two shifts per day, seven days a week, since the end of March 2020.

Earlier press release: 鈥淔olding of SARS-CoV2 genome reveals drug targets 鈥� and preparation for 鈥淪ARS-CoV3"

Scientific contact:
Professor Harald Schwalbe
Institute for Organic Chemistry and Chemical Biology
Center for Biomolecular Magnetic Resonance (BMRZ)
51猎奇
Tel +49 69 798-29137
schwalbe@nmr.uni-frankfurt.de

Jul 1 2021

10:54

51猎奇 study on student learning outcomes during COVID-19-related school closures in spring 2020

Effects of remote learning during first lockdown comparable to summer vacation

How effectively do children and teenagers learn in remote classes from home? The issue has been the subject of intensive discussions, not only among experts. A systematic review from the Department of Educational Psychology at 51猎奇 provides a sobering answer for the spring of 2020. The situation seems to have later improved.

FRANKFURT. Despite diverse efforts to continue school operations as far possible with the help of remote learning and digital options during COVID-19-related schools closures, large deficits came about in the learning progress of many students. This was shown by a systematic review from Education Psychology at 51猎奇. In the course of this systematic review, scientific databases were used to identify studies worldwide that examined the effect of COVID-19-related school closures on student achievement.

鈥淲e only included publications with appropriate research methods that allow evidence-based conclusions about the effect of COVID-19-related schools closures on student achievement, and that used testing instruments that are suitable for measuring student achievement," explains Professor Andreas Frey, who teaches Educational Psychology with a focus on consulting, measurement and evaluation at 51猎奇, and is one of the authors of the study. This showed that, compared to pre-COVID-19 in-person teaching, average student achievement was significantly lower during school closures. 鈥淭he average student achievement during the school closures in the spring of 2020 is best designated as stagnation, with a tendency toward losses comparable in size to the effect of summer vacation," says Frey. Observed losses in learning were particularly distinct for students from socio-economically disadvantaged homes. 鈥淭he empirical evidence supports previous assumptions: The gap between rich and poor widened even more during the first COVID-19-related school closures," concludes Frey. However, there are also initial indications that the effects of the later school closures from winter 2020/21 onwards may not necessarily be as drastic. Online teaching has improved in many places, which seems to mitigate the negative effects.

The systematic review written by Svenja Hammerstein, Christoph K枚nig, Thomas Dreis枚rner and Andreas Frey is available as an open access preprint at https://psyarxiv.com/mcnvk/. The work is part of the project "Identifying and Reducing COVID-19-related Educational Disadvantages" (CoBi), which is funded by the Beisheim Foundation and the Goethe Coronavirus Fund. In the CoBi project, an online screening tool is being developed to identify particularly at-risk secondary school students, who are then supported by the MainKind counselling centre at 51猎奇.

Publication:

Further information

Professor Andreas Frey
Educational Psychology with a focus on consulting, measurement and evaluation
frey@psych.uni-frankfurt.de

Jun 24 2021

14:31

Screening of multiple gene mutations is also applicable for complex nervous and immune diseases

New technique for studying cancer mutations 鈥� approaches for future therapies

An extended application of the CRISPR-Cas technology has been made possible by Dr Manual Kaulich's team at 51猎奇: the new 3Cs multiplex technique allows the effect of genetic changes in any two genes to be studied simultaneously in cell cultures. This can provide important clues for the development of therapies to treat cancer or diseases of the nervous and immune systems.

FRANKFURT. Cancer and many other diseases are based on genetic defects. The body can often compensate for the defect of one gene; it is only the combination of several genetic errors that leads to the clinical picture. The 3Cs multiplex technique based on CRISPR-Cas technology developed at 51猎奇 Frankfurt now offers a way to simulate millions of such combinations of genetic defects and study their effects in cell culture. These "gene scissors" make it possible to introduce, remove and switch off genes in a targeted manner. For this purpose, small snippets of genetic material ("single guide RNA") are used as "addresses" that guide the gene scissors to specific sections of the DNA, where the gene scissors then become active.

The scientists from the Institute of Biochemistry II at 51猎奇 have expanded the 3Cs technique that they developed and patented three years ago. 3Cs stands for covalently-closed circular-synthesised, because the RNA elements used for CRISPR-Cas are generated with the help of a circular synthesis and are thus distributed more uniformly. With a whole library of such RNA rings, any gene in a cell can be specifically addressed in order to change it or switch it off.

The new 3Cs multiplex technique now even allows the simultaneous manipulation of two genes in one cell. Dr. Manuel Kaulich explains: "We can produce 'address' RNA libraries for all conceivable two-gene combinations. This allows up to several million combinations to be tested simultaneously in one experiment."

Until now, the cost and effort of such experiments was very high; the research group's new technique reduces it, including costs, by a factor of ten. This is because the team can produce the address libraries very uniformly and in high quality thanks to the new 3Cs multiplex technique. "Due to the mediocre quality of the CRISPR-Cas libraries previously available, very large experiments always had to be carried out to statistically compensate for any errors that arose," says Kaulich.

Using the example of various genes involved in degradation processes, the research group demonstrated the potential of the new 3Cs multiplex technique: they examined almost 13,000 two-way combinations of genes that are responsible for recycling processes (autophagy) in the cell. With their help, the cell breaks down and recycles "worn-out" cell components. Disturbances in autophagy can trigger cell proliferation.

"Using the 3Cs multiplex technique, we were able to identify, for example, two genes involved in autophagy whose switching off leads to an uncontrolled growth of cells," explains Kaulich. "These are precisely the autophagy mutations that occur in every fifth patient with squamous cell carcinoma of the lung. In this way, we can search very efficiently in cell culture experiments for genes that play an important role in cancer, and also in diseases of the nervous and immune systems, and that are suitable as possible targets for therapies."

The 51猎奇 research group has applied for a patent for its developments through the university's technology transfer subsidiary Innovectis. The start-up company Vivlion GmbH, spun off from the Institute of Biochemistry II with the participation of Manuel Kaulich, is already offering the use of this technology on the market.

Publication: Valentina Diehl, Martin Wegner, Paolo Grumati, Koraljka Husnjak, Simone Schaubeck, Andrea Gubas, Varun Jayeshkumar Shah, Ibrahim H Polat, Felix Langschied, Cristian Prieto-Garcia, Konstantin M眉ller, Alkmini Kalousi, Ingo Ebersberger, Christian H Brandts, Ivan Dikic, Manuel Kaulich, Minimized combinatorial CRISPR screens identify genetic interactions in autophagy. Nucleic Acids Research, gkab309,

Further information:
Dr Manuel Kaulich
Institute for Biochemistry II
51猎奇 Frankfurt
Tel: +49 69 6301-6295
kaulich@em.uni-frankfurt.de

Dr Kerstin Koch
Institute for Biochemistry II
51猎奇 Frankfurt
Tel.: +49 696301-84250
k.koch@em.uni-frankfurt.de

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Department, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de

Jun 10 2021

13:33

German Research Foundation funds new CRC Transregio 326 鈥濭eometry and arithmetic of uniformized structures鈥� 鈥� CRC 1039 on medical signal path research enters third funding period 鈥� 51猎奇 involved in two further CRC-Transregios

Funding decision on four collaborative research centres at 51猎奇: new CRC for basic research in mathematics

Researching intricate geometric and arithmetic objects is the goal of the new Collaborative Research Centre Transregio 326 (TRR 326), coordinated by 51猎奇. On 25th May, the German Research Foundation (DFG) announced that the TRR 326 would be funded with 9.2 million euros for the next four years. The CRC 1039 鈥淪ignalling by fatty acid derivatives and sphingolipids in health and disease", for which Goethe University is spokesperson, will be continued and receive 9.6 million euros for the third funding period. Two other TRRs in which 51猎奇 is involved will also be funded by the DFG: In the TRR 211 鈥淪trongly interacting matter under extreme conditions", the spokesperson will switch from 51猎奇 to the Technical University of Darmstadt (9.2 million euros). Finally, scientists from 51猎奇 are also significantly involved in TRR 301 "The tropopause region in a changing atmosphere" (spokesperson: Johannes Gutenberg University Mainz, 鈧�12.3 million).

FRANKFURT. Professor Enrico Schleiff, President of 51猎奇 Frankfurt, congratulates the scientists on their success: "51猎奇's commitment, particularly in the Transregio Collaborative Research Centres, demonstrates our excellent scientific networking in the region, especially in the natural sciences and medicine. The association of the Rhine-Main universities of Frankfurt, Mainz and Darmstadt, have given this regional cooperation a framework: There are now more than 30 research associations and networks in this strategic alliance, and last year we established the RMU degree programme so that talented students can also benefit from RMU."

The mathematical exploration of complicated geometric and arithmetic spaces with the help of uniformization is the research topic of TRR 326 "Geometry and arithmetic of uniformized structures - GAUS". Together with coordinator 51猎奇 Frankfurt, the Technical University of Darmstadt and Heidelberg University successfully applied for TRR 326; associated institutions are the Johannes Gutenberg University Mainz and the Technical University of Munich. The concept of uniformization goes back to ideas of Felix Klein and Henri Poincar茅 from the 19th century and seeks a uniform description of certain geometric objects. A very simple example uniformization can be illustrated with the slinky, a metal spiral toy which is able to "run" down a staircase doing "somersaults". When pressed together, it has - seen from above - the geometry of a circle. This circle can be uniformized by pulling the metal spiral apart. It becomes particularly simple when the spiral is completely unwound and, geometrically, is only a simple wire. In order to preserve the information of the slinky, each spiral turn on the wire is marked with a colour dot, which gives the wire a shifting symmetry (you change levels in the spiral). A globally complicated geometric space (in our example, the circle of the slinky) is replaced by a much simpler space (here a straight line) without changing the local structure. The original complexity is described by internal symmetries (illustrated in the example by periodic markings) of the simpler space.

In TRR 326 GAUS, mathematicians deal with uniformization of very complicated geometric spaces - this includes modern geometric concepts, in particular tropical and p-adic geometries - and with analogous applications of the uniformization technique to arithmetic (number-theoretic) questions. Here, the researchers try to identify fundamental connections, for example to moduli spaces, automorphic forms, Galois representations, and cohomological structures. Professor Jakob Stix, mathematician at 51猎奇 and GAUS spokesman, says: "With the SFB Transregio GAUS, we are building on the extremely successful collaboration between TU Darmstadt and 51猎奇 in the LOEWE priority 'Uniformed Structures in Arithmetic and Geometry' and the DFG research group 'Symmetry, Geometry and Arithmetic' at TU Darmstadt and Heidelberg University. I am very much looking forward to doing joint research with so many outstanding colleagues."

The Collaborative Research Centre 1039 "Signalling by fatty acid derivatives and sphingolipids in health and disease," which 51猎奇 is now continuing together with the Max Planck Institute for Heart and Lung Research in Bad Nauheim, is entering its third funding period. The scientists are studying a group of poorly water-soluble biomolecules, the lipids. As lipid bilayers, they prominently form the membranes that surround our cells and also divide the interior of the cells. As fats, they serve as energy storage for our bodies.

However, CRC 1039 is investigating a function that is still comparatively under-researched: Lipids are part of many signalling pathways through which cells regulate growth and metabolism and communicate with their environment. Dysregulated lipids are apparently decisively involved in the development and progression of diseases such as diabetes, cancer, inflammation, and neurodegenerative diseases. After fundamental work in the first two funding periods, the third funding period focuses on understanding the whole organism. Professor Josef Pfeilschifter, pharmacologist at 51猎奇 and spokesman of SFB 1039, explains: "We want to understand the lipid signalling network as a whole and thus develop innovative ways to diagnose and treat a wide variety of diseases related to dysregulated lipids. In doing so, we can rely on a long-standing and broad expertise in 'lipid signalling', which is also founded on the establishment of sophisticated analytical methods based on mass spectrometry."

Scientists from 51猎奇 are significantly involved in two other CRC Transregios:

How matter behaves under conditions of extreme pressure and temperature, in which atoms overlap and fuse with each other is being investigated by TRR 211 "Strongly interacting matter under extreme conditions", which is entering its second funding period. For extremely short periods of time, such states of matter can be created in particle accelerators, revealing something about the strong interaction that holds atomic nuclei together. In the cosmos, such extreme states of matter occur when, for example, neutron stars collide with each other. Besides51猎奇, the Technical University of Darmstadt, which is the new host university, and Bielefeld University are also involved in this collaborative research centre.

In the new TRR 301 "The tropopause region in a changing atmosphere", atmospheric scientists will study the tropopause region: the zone in the atmosphere that separates the lower "weather layer" (troposphere) from the stratosphere above. The research focus is on the physical and chemical processes of this region and their influence on planetary circulation and climate. The main locations are the Johannes Gutenberg University Mainz (spokesperson) and 51猎奇 Frankfurt. Also involved are the Technical University of Darmstadt, the Ludwig Maximilian University of Munich, the Max Planck Institute for Chemistry in Mainz, the J眉lich Research Centre and the German Aerospace Centre (DLR) in Oberpfaffenhofen.

Image for download:

Caption: Using the mathematical technique of uniformization, complicated geometric spaces (here: the j-invariant as an automorphic function on the uniformization of the moduli space of elliptic curves) can be represented as highly symmetric geometric patterns. Credit: Michaelis Neururer

Further information:

Professor Jakob Stix
Spokesman TRR 326 鈥濭AUS鈥�
Institute for Mathematics
51猎奇 Frankfurt
Tel: +49 69 798-28998
stix@math.uni-frankfurt.de

Professor Josef Pfeilschifter
Spokesman SFB 1039 鈥淪ignalling by fatty acid derivatives and sphingolipids in health and disease"
Institute for General Pharmacology and Toxicology
51猎奇 Frankfurt
Tel. +49 69 6301-6950
pfeilschifter@em.uni-frankfurt.de

TRR 211 鈥濻trongly interacting matter under extreme conditions鈥�

TRR 301 鈥濼he tropopause region in a changing atmosphere鈥�

May 27 2021

10:34

Fear of long-term consequences 鈥� physical activity could actually help to better manage the pandemic

Physical activity levels and well-being sink worldwide during coronavirus restrictions 鈥� study led by Goethe University聽

During the first lockdown people were a good 40 percent less active, as shown by an international study led by 51猎奇 Frankfurt. Psychological well-being sank as well; the portion of people at potential risk for depression tripled. The authors fear long-term consequences and urge that this be taken into account going forward.

FRANKFURT. Twenty scientists from 14 countries warn of a hidden 鈥減andemic within the pandemic鈥� in two current publications. On the one hand, physical activity levels have gone down significantly, on the other hand, psychological well-being has suffered. 鈥淕overnments and those responsible for health systems should take our findings seriously," emphasizes the author team, headed by Dr Jan Wilke from the Institute for Sport Sciences at 51猎奇 Frankfurt.

About 15,000 people in participating countries answered standardised questionaires as part of an international survey. In April/May 2020, they reported physical activity levels (13,500 participants) as well as their mental and physical well-being (15,000 participants) before and during the pandemic-related restrictions.

Older individuals especially affected

鈥淭he results show drastic reductions in physical activity and well-being," says Wilke. More than two thirds of those questioned were unable to maintain their usual level of activity. Moderate exercise decreased by an average of 41 percent according to self-reported data - this includes anything that increases heart rate and breathing, such as brisk walking, running, cycling or even strenuous gardening.

The proportion of vigorous exercise during which people sweat and clearly run out of breath fell by a similar amount (42 percent). The effects were somewhat higher among professional athletes and particularly active people, as well as comparatively young and old people. The decline in activity was particularly noticeable among people over 70 years of age, who were 56 to 67 percent less active than before. "We know that physical inactivity, especially in older people, can lead to changes that are difficult to reverse after only two weeks - for example, in body fat percentage or insulin sensitivity," warn the study authors.

Exercise helps prevents disease and reduces mortality

The WHO recommends at least 150 minutes of moderate or 75 minutes of intensive physical activity per week - 81 percent of the study participants achieved this before the pandemic, but only 63 percent during the lockdowns. Yet sufficient exercise can reduce mortality by up to 39 per cent, as a 2015 study showed. Data suggests that too little exercise plays a role in about one in ten premature deaths, because physical activity reduces the likelihood of, for example, high blood pressure, metabolic disorders such as type 2 diabetes, and cancer.

Exercise is known to activate the immune system because it promotes blood circulation and activates lymphocytes and messenger substances (cytokines) that are important for immune defence. Studies show that physically active people are less susceptible to influenza, rhino and herpes viruses and respiratory infections in general. So it may be that exercise also offers protection against severe COVID-19 by reducing risk factors such as obesity. Physical health and exercise also reduce the risk of mental health problems such as depression and anxiety disorders.

Mental well-being drastically reduced

In another part of the study, the team of authors asked about mental well-being during the pandemic restrictions. 73 percent of the study participants stated that their well-being had deteriorated. The perceived quality of life as measured by the WHO well-being Index, which measures mood, relaxation, activity, rest and interest, dropped on average from 68 percent before the pandemic to 52 percent during the first lockdown phase.

Above all, people felt less "active and full of energy" and led a life less "filled with interesting things". The proportion of very low scores indicating a possible risk of depression tripled from 15 to 45 percent. "These effects were stronger among women and younger people, " the study says. "More attention should be paid to the needs of women in particular, as they are significantly more vulnerable."

Nonetheless, 14 to 20 percent of the respondents also stated that their health had improved - the authors see more family time, greater work autonomy, fewer business trips or a changed perception of health as possible reasons. "But a large part of the population may still be suffering from barely visible health effects of the pandemic," the team of authors warns.

This could also translate into rising health costs: According to US data, the annual expenditure for inactive or insufficiently active people increases by 1200 and 600 euros respectively - this would add up to two to four million euros after one year just for the 3104 people from the survey who did not exercise enough during the lockdown.

The results of these first multinational studies are likely to be relevant for an estimated four billion people worldwide who were affected by the restrictions of the first coronavirus wave in the spring of 2020. However, the data was predominantly collected through electronic media, so populations without internet were not included. Also, no differentiation was made according to factors such as living environment, education and social status. In addition, the data is based on self-assessments, not measurements, which may distort retrospective perceptions in particular. "Nevertheless, our results show that the issues of physical activity and well-being belong on the policy agenda," Wilke emphasises.

"Governmental and health-related decison-makers need to develop strategies to mitigate the loss of physical activity," write the authors. They suggest better public education, creating exercise opportunities with a low likelihood of infection, or offering effective home exercise programmes. Among numerous other health facets, this would have a particularly positive effect on mental well-being.

Negative effects similar to those observed in these studies should be avoided at all costs in future pandemics. "Unfortunately, physical activity and exercise do not have a strong lobby and are usually neglected in public discourse," says Wilke. "Yet they can greatly help us to better cope with the pandemic."

Publications: Jan Wilke et al. A Pandemic within the Pandemic? Physical Activity Levels Substantially Decreased in Countries Affected by COVID-19. Int. J. Environ. Res. Public Health, Vol. 18, 5 (2021),

Jan Wilke et al., Drastic Reductions in Mental Well-Being Observed Globally During the COVID-19 Pandemic: Results from the ASAP Survey. Front. Med. 8:578959 (2021),

Further information
Dr Jan Wilke
Institute f眉r Sport Sciences
51猎奇 Frankfurt
Tel. +49 (69) 798-24588,
wilke@sport.uni-frankfurt.de

Editor: Dr Markus Bernards, Science Editor, PR & Communication Department, Tel: +49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de