Goethe-Universit盲t 鈥� Press releases

51猎奇 PR & Communication Department聽

Sep 17 2024

10:00

Award recognizes the discovery of a fundamental signaling pathway of innate immunity聽

Andrea Ablasser, Glen Barber, and Zhijian J. Chen will be awarded the Paul Ehrlich and Ludwig Darmstaedter Prize 2025聽

Physician Andrea Ablasser from the 脡cole polytechnique f茅d茅rale de Lausanne, virologist Glen Barber from Ohio State University and biochemist Zhijian 'James' Chen from the University of Texas Southwestern Medical Center at Dallas will receive the Paul Ehrlich and Ludwig Darmstaedter Prize 2025, the Scientific Council of the Paul Ehrlich Foundation announced today. The award honors the prizewinners' discovery of the cGAS-STING signaling pathway, i.e. the alarm system that sounds when, in the event of infection, cancer or cellular stress, DNA enters a cell's plasma. Once this happens, the police of the innate immune system is immediately called into action. Drugs interfering with this signaling pathway are currently under development.

FRANKFURT. It is extremely dangerous when, in response to either viral intruders or damage within the cell itself, DNA appears in the cytoplasm of a cell. Our immune system is then called upon to react immediately and initiate defensive measures. Just how it manages to do this is what the prizewinners researched and learned between 2008 and 2013 and have since been able to clarify more and more comprehensively. What they discovered are the stations and signals of an intracellular alarm system without which we could not survive. "The cGAS-STING signaling pathway is a foundation of our innate immune defense that has long been sought after," explains Prof. Thomas Boehm, chairman of the Paul Ehrlich Foundation's Scientific Council. "With their discovery, the award winners have opened up the possibility for medicine to treat infections, cancer and inflammatory diseases more effectively than before."

Ilya Mechnikov had already reported that nucleic acids such as DNA can trigger an immune reaction in 1908, when he was awarded the Nobel Prize for Medicine, which he shared with Paul Ehrlich. How this reaction takes place at the molecular-biological level only began to be clarified one hundred years later, in 2008, when Glen Barber and his team discovered a protein, that he called STING. This protein is anchored in the membrane of the cell's extensive tubular system, the endoplasmic reticulum (ER). Once an infection with DNA viruses occurs, STING commands certain genes in the cell nucleus to immediately start producing interferons. It is therefore, as the abbreviation says, a STimulator of INterferon Genes. The interferons are distributed in the surrounding tissue and stimulate the production of phagocytes and natural killer cells as well as other immune messengers.

How STING learned that DNA has appeared in the cytoplasm remained a mystery until 2012, when Zhijian 'James' Chen and his team solved it. With extraordinary biochemical sophistication, Chen isolated and identified a small ring-shaped molecule 鈥� cyclic guanosine monophosphate adenosine monophosphate (cGAMP) 鈥�, which consists of two nucleotides and is capable of activating STING, and later succeeded at doing the same for the enzyme cGAS, which catalyzes the formation of cGAMP. In 2013, Andrea Ablasser characterized cGAMP in detail and showed that its production and structure differ chemically from those of other dinucleotides. Ablasser was awarded the Paul Ehrlich and Ludwig Darmstaedter Early Career Award 2014 for this achievement.

The prizewinners' discoveries provide the following overall picture: The enzyme cGAS acts as a sensor for DNA in the cytoplasm. It clasps the DNA strands. Thereby it is enabled to change its conformation in such a way that it can produce the chemically unique messenger substance cGAMP from the molecules GTP and ATP, which are abundant in the cell's interior. cGAMP in turn triggers the transducer STING, which then brings other signal molecules into the alarm chain. The target of this relay is the genes in the cell nucleus, according to whose plan interferons and other immune messengers are produced.

Over the past decade, the three prizewinners have mapped the branches of the signaling pathway they discovered in ever greater detail, paying particular attention to the fact that the cGAS sensor does not differentiate between foreign and own DNA. This makes sense, considering that the cell's own DNA normally only occurs in the cell nucleus and in the mitochondria. If it leaks into the cytoplasm, as in cancer cells for example, cGAS has to kick in and switch on the immune defense. However, this is also risky because it can lead to unfounded immune attacks on the body 鈥� something against which our cells have effective protective mechanisms. However, the older we get, the more likely these mechanisms are to fail. This explains the rising incidence of non-infectious inflammations, also known as sterile inflammations, which are the basis of classic autoimmune, cardiovascular and neurodegenerative diseases, including Parkinson's. Sterile inflammations are characterized by an overactive cGAS-STING signaling pathway.

Substances that inhibit this signaling pathway therefore have great therapeutic potential and play an important role in the research of many pharmaceutical companies. Andrea Ablasser succeeded in synthesizing the first STING inhibitor in 2018.Agonists of this signaling pathway are not only being tested in vaccine development, but also as cancer drugs, and show strong preclinical antitumor effects in combination with checkpoint inhibitors.

Andrea Ablasser, born 1983, is Professor of Food Science at the 脡cole polytechnique f茅d茅rale de Lausanne in Switzerland.

Glen Barber, born 1962, is Professor in the Department of Surgery and Director of the Center for Innate Immunity and Inflammation, Pelonia Institute for Immuno-Oncology at the Ohio State University, Columbus, Ohio, USA.

Zhijian J. Chen, born 1966, is George L. MacGregor Distinguished Chair in Biomedical Science, Howard Hughes Medical Investigator and Professor of Molecular Biology at the University of Texas' Southwestern Medical Center in Dallas, USA.

Photos of the award winners are available for use and can be downloaded at .

Detailed background information "When DNA triggers an alarm" is available at

The prize will be awarded on March 14, 2025 at 5 p.m. by the Chairman of the Scientific Council of the Paul Ehrlich Foundation in Frankfurt's Paulskirche. We kindly ask you to take this into account when planning your schedule. Please do not hesitate to contact us if you have any questions.

Further information
Press Office Paul Ehrlich Foundation
Joachim Pietzsch
Phone: +49 (0)69 36007188
E-mail: j.pietzsch@wissenswort.com

Sep 16 2024

14:38

Science network makes its debut at upcoming science festival held on Frankfurt鈥檚 central Ro脽markt square, promising amazement, questions, discussions and exchange

Setting the stage for the 鈥淔rankfurt Alliance鈥�

FRANKFURT. In January 2024, 16 Frankfurt-based research institutions joined forces to set up the 鈥淔rankfurt Alliance鈥�, made up of 51猎奇 Frankfurt and several non-university research institutions. With the aim of visualizing at an event held in the heart of the Main metropolis both the strength and the diversity of research conducted in the science city of Frankfurt and the larger Rhine-Main region, including its importance for society, the alliance invites you to the first 鈥淪cience Festival鈥�, held

on Saturday, September 28, from 10 a.m. to 7 p.m.
at Ro脽markt
in downtown Frankfurt.

The big and colorful family festival will bring science to life in multiple tents as well as on stage. Its diverse program ranges from science slams to debates on current socio-political topics and hands-on activities all the way to short lectures and musical performances. Researchers from different 51猎奇 faculties as well as the research-intensive institutes of Max Planck Society, Leibniz Association, Fraunhofer Society, Helmholtz Association, Paul-Ehrlich-Institut and the German Cancer Consortium will be providing insights into their research and will be on hand to answer questions and engage in discussion.

The program on stage will kick off with a panel discussion on the topic of (educational) justice, joined by DIPF | Leibniz Institute for Research and Information in Education. The discussion will focus not only on the connection between educational opportunities and social background, but also on social mobility and the important roles played by politics and research in decision-making processes. A comprehensive AI quiz in the form of a prompt battle, a talk and comedy interludes by the two quirky 鈥減rofessors鈥� Dr. KNOW and Dr. HOW are also part of the program. Together with biologists and equipped with a magnifying glass, you can explore Ro脽markt鈥檚 nooks and crannies, and discover what exactly is growing between the pavement joints and wall cracks. Wrapping up the festival will be a rap by Coodiny, aka Nikita Kudakov and his live band. Kudakov has been making music since he was a teenager and is now a doctoral candidate at the Max Planck Institute for Empirical Aesthetics, where he is researching the interaction between rappers and their audience. The stage program will be moderated by Stephan H眉bner from hr Info, the festival's media partner.

Accompanying the program on stage, each of the alliance鈥檚 member institutions will have their own pagoda tent, offering insights into respective research activities. To name a few examples: In a joint tent, Max Planck Institute for Heart and Lung Research and 51猎奇 Frankfurt will be presenting a walk-in model of the human heart, a central research object of the Cardio-Pulmonary Institute (CPI) cluster of excellence, which is dedicated to diseases of the cardiovascular system. The adjacent 51猎奇 tent will feature colorful flowers in bloom, as well as open studios for experimenting, painting and solving puzzles. In addition, scholars from the humanities, social and natural sciences will be presenting their own favorite topics as part of the series 鈥淩esearch close to my heart鈥�. Visitors to the Senckenberg Society for Nature Research鈥檚 tent will be able to travel around the world and evaluate camera traps from Bolivia and South Africa, while the Peace Research Institute Frankfurt (PRIF) will use the festival to collect visitors鈥� ideas for peace. As part of its 鈥淒ive into the cell鈥� activity, the Max Planck Institute for Biophysics is providing VR glasses that enable visitors to experience the building blocks of life from the inside, while two hands-on experiments from GSI Helmholtzzentrum f眉r Schwerionenforschung show how particle accelerators work.

The festival invites passersby of all ages to not only be curious, but to join in the conversations, ask questions and learn more about science. Catering to visitors鈥� culinary tastes will be food trucks serving regional specialties, while numerous deckchairs and seats invite passersby to stay and linger. The festival starts at 10 a.m. and ends at 7 p.m. Admission is free.

The full program and further information is available at:

Further information:
frankfurtalliance@uni-frankfurt.de

Sep 4 2024

14:08

Alleviating the long-term effects of a SARS-CoV-2 infection

Post-COVID Syndrome: Government-funded drug study gets underway

An innovative study for the treatment of post-COVID syndrome (PCS) is starting under the direction of Frankfurt University Hospital鈥檚 Department of Infectious Diseases. The research project, funded by the German Federal Ministry of Education and Research (BMBF), will investigate new ways of alleviating the long-term effects of COVID-19, including fatigue and cognitive impairment. The first patient has been enrolled in the study this week.

鈥淭here is still an urgent need for the treatment of post-COVID and associated symptoms,鈥� says Prof. Dr. Maria Vehreschild, who heads the study and oversees Frankfurt University Hospital鈥檚 Infectious Diseases Department. 鈥淭hat is why we are pleased to conduct RAPID_REVIVE, the first adaptive clinical study within the Network of University Medicine.鈥� The German Network of University Medicine (NUM) was set up in 2020 as part of the country鈥檚 COVID-19 pandemic crisis management to coordinate clinical COVID-19 research at German university hospitals.

RAPID_REVIVE (Randomized Adaptive Assessment of Post COVID Syndrome Treatments_Reducing Inflammatory Activity in Patients with Post COVID Syndrome) is a phase 2, adaptive, randomized, placebo-controlled, and double-blind clinical trial sponsored by 51猎奇 Frankfurt and funded by the Federal Ministry of Education and Research (BMBF) as part of NUM. The structural conditions required to commence the study were created as part of the NUM project 鈥淣APKON Therapeutic Intervention Platform鈥� (NAPKON-TIP). A total of 376 patients at eleven different NAPKON locations will be included in the study.

Post-COVID Syndrome
The World Health Organization (WHO) estimates that most people who have had COVID-19 recover fully. However, after overcoming the infection, a subset of those affected suffer long-term effects, known as post-COVID syndrome (PCS). PCS is defined by symptoms that remain even three months after the onset of COVID-19, that continue for at least two months thereafter and that cannot be explained by another diagnosis. While the symptoms are diverse, those affected by PCS often suffer from pronounced fatigue, shortness of breath as well as cognitive impairments.

The RAPID_REVIVE study examines changes in the physical functions of participants, which are recorded at different points in time using questionnaires and tests. Beyond that, the study also looks at general mental and physical health, fatigue, cognitive functions, the severity of mental health impairments, shortness of breath and physical resilience. The study also seeks to identify prognostic biomarkers that provide information about the individual progression of PCS, which should pave the way for the selection of a treatment strategy tailored to the individual patient.

Vidofludimus calcium: Testing a promising drug candidate
Study participants will receive either the drug vidofludimus calcium (IMU-838) or a placebo. The decision as to who receives which preparation is randomly made (blinded 1:1 randomization). Once 150 patients have been included in the study, the allocation will be adjusted in accordance with the study鈥檚 interim evaluations. Vidofludimus calcium is a novel drug candidate that activates the neuroprotective transcription factor Nurr1, a novel target for neurodegenerative diseases. In addition, the drug inhibits the enzyme DHODH, thereby blocking the production of pyrimidines, which cells rely on primarily for RNA synthesis. It is particularly effective in highly activated immune cells as well as virus-infected cells, which have a high demand for pyrimidines. Administering vidofludimus calcium could also help in treating chronic inflammatory and autoimmune diseases, since the drug reduces excessive inflammation and prevents viral infection and reactivation.

Vidofludimus calcium showed promising results in an earlier clinical trial involving COVID-19 patients: Those who received the drug recovered faster and suffered less long-term fatigue compared to those who received a placebo. The treatment was well tolerated with few side effects. Vidofludimus calcium could thus not only help with the acute treatment of COVID-19, but also alleviate long-term symptoms.

鈥淲e hope the RAPID_REVIVE study will constitute a significant advance in the treatment of post-COVID syndrome. Thanks to the successful implementation within the NAPKON-TIP structures, the platform should provide an established structure available to NUM and external parties for future adaptive studies 鈥� which will enable us to react flexibly to new findings and ensure the best possible patient care,鈥� says Prof. Dr. Maria Vehreschild, adding: 鈥淲e look forward to receiving the results of this groundbreaking study and evaluating its potential impact on future therapeutic approaches.鈥�

Links:
Study at German Network of University Medicine (NUM) (in German)

German Network of University Medicine (NUM)

WHO information on post-COVID 19 condition (long COVID):

Further information
Prof. Dr. Maria Vehreschild
Medical Clinic 2
Head of the Infectious Diseases Department
Frankfurt University Hospital
Tel: +49 69 63 01 鈥� 66 08
E-Mail: maria.vehreschild@ukffm.de

51猎奇

Press releases 鈥� September 2024

51猎奇 PR & Communication Department聽

Andrea Ablasser, Glen Barber, and Zhijian J. Chen will be awarded the Paul Ehrlich and Ludwig Darmstaedter Prize 2025聽

Setting the stage for the 鈥淔rankfurt Alliance鈥�

Post-COVID Syndrome: Government-funded drug study gets underway