Doctor Andrea Ablasser from the École polytechnique fédérale de Lausanne, virologist Glen Barber from Ohio State University and biochemist Zhijian ‘James’ Chen from the University of Texas Southwestern Medical Center in Dallas will receive the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize. The Board of Trustees of the Paul Ehrlich Foundation announced this today. The prizewinners discovered the cGAS-STING signaling pathway. This is the alarm system that goes off when DNA enters the plasma of a cell in the event of infections, cancer or cellular stress. It immediately calls the police of the innate immune system into action. Drugs that intervene in this signaling pathway are currently being developed.
Photo: Paul Ehrlich Foundation / (Photo Ablasser: Titouan Veuillet/EPFL Photo Barber: Ohio State University Photo Chen: Mei-Chun Jau/UT Southwestern Medical Center)
The appearance of DNA in the cytoplasm of a cell represents a major threat. It is caused either by viral invaders or by damage within the cell itself. Our immune system must react immediately and initiate defensive measures. The prize winners discovered how it does this between 2008 and 2013 and have since then explained it in ever greater detail. They discovered 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 defenses, and has been sought for a long time,” explains the chairman of the foundation’s board, Prof. Thomas Boehm. “With their discovery, the prize winners have opened up the possibility of treating infections, cancer and inflammatory diseases more effectively than before.”
Ilya Mechnikov had already reported in 1908, when he was awarded the Nobel Prize in Medicine, which he shared with Paul Ehrlich, that nucleic acids such as DNA can trigger an immune reaction. How this reaction takes place in molecular biology only began to become clear a hundred years later, when Glen Barber and his group discovered a protein in 2008 that he named STING. This protein is anchored in the membrane of the extensive tubular system of the cell, the endoplasmic reticulum (ER). After an infection with DNA viruses, this protein directs certain genes in the cell nucleus: it immediately produces interferons. So, as the abbreviation says, it is a STsimulator of INterferon-Genen. The interferons spread in the surrounding tissue and stimulate the formation of phagocytes and natural killer cells as well as other immune messengers. How STING learns that DNA has appeared in the cell plasma remained a mystery until 2012, when Zhijian ‘James’ Chen and his group solved it. With extraordinary biochemical sophistication, Chen isolated and identified a small ring-shaped molecule made up of two nucleotides that is able to activate STING – cyclic guanosine monophosphate adenosine monophosphate (cGAMP) – and then the enzyme cGAS, which catalyzes the formation of cGAMP. In 2013, Andrea Ablasser characterized cGAMP in detail and showed that it is chemically different from other dinucleotides in terms of production and structure. For this achievement, she was awarded the Paul Ehrlich and Ludwig Darmstaedter Young Researcher Prize in 2014.
The following overall picture emerged from the prize winners’ discoveries: The enzyme cGAS acts as a sensor for DNA in the cell plasma. It grips the DNA strands. This causes it to deform in such a way that it can produce the chemically unique messenger substance cGAMP from the GTP and ATP molecules that are abundant inside the cell. cGAMP in turn controls the signal converter STING, which then includes other signal molecules in the alarm relay. The target of this relay are those genes in the cell nucleus according to whose plan interferons and other immune messengers are produced.
Over the past decade, the three prize winners have mapped the branches of the signaling pathway they discovered with increasing precision. They paid particular attention to the fact that the cGAS sensor does not distinguish between foreign and one’s own DNA. This makes sense because one’s own DNA is normally only found in the cell nucleus and mitochondria. If it leaks into the cytoplasm, as in cancer cells, for example, cGAS must kick in and activate the immune system. But this is also risky because it can lead to unfounded immune attacks on the body. Our cells have effective protective mechanisms against this. The older we get, however, the more likely these mechanisms are to fail. This is why inflammations that are not caused by infection are becoming more and more common. They are also known as sterile inflammations and are the basis for classic autoimmune diseases as well as cardiovascular diseases and neurodegenerative diseases such as 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. Conversely, agonists of this signaling pathway are not only being tested in vaccine development, but also as cancer drugs. In combination with checkpoint inhibitors, they show strong preclinical antitumor effects.
Andrea Ablasser, Born in 1983, she is a professor of food science at the École polytechnique fédérale de Lausanne in Switzerland.
Glen Barber, Born in 1962, he is a professor in the Department of Surgery at Ohio State University, Columbus, Ohio, USA, where he heads the Center for Innate Immunity and Inflammation.
Zhijian J. Chen, Born in 1966, he is the 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.
The Paul Ehrlich and Ludwig Darmstaedter Prize is the most prestigious medical award in Germany. It is endowed with 120,000 euros and is traditionally awarded on Paul Ehrlich’s birthday, March 14, in the Paulskirche in Frankfurt. It honors scientists who have made special contributions to the research field represented by Paul Ehrlich, particularly in immunology, cancer research, hematology, microbiology and chemotherapy. The prize, which has been awarded since 1952, is financed by the Federal Ministry of Health, the Association of Research-Based Pharmaceutical Manufacturers and by earmarked donations from the following companies, foundations and institutions: Else Kröner-Fresenius Foundation, Sanofi-Aventis Deutschland GmbH, CH Boehringer Sohn AG & Co. KG, Biotest AG, Hans and Wolfgang Schleussner Foundation, Fresenius SE & Co. KGaA, F. Hoffmann-LaRoche Ltd., GSK GlaxoSmithKline GmbH & Co. KG, Grünenthal Group, Janssen-Cilag GmbH, Merck KGaA, Bayer AG, Georg von Holtzbrinck GmbH & Co.KG,, B. Metzler seel. Sohn & Co KGaA. The prize winners are selected by the Board of Trustees of the Paul Ehrlich Foundation. A list of the Board of Trustees members is available on the Paul Ehrlich Foundation website.
Die Paul Ehrlich Foundation is a legally dependent foundation that is administered in trust by the Association of Friends and Supporters of Goethe University. The honorary president of the foundation, which was established in 1929 by Hedwig Ehrlich, is Professor Dr. Katja Becker, President of the German Research Foundation, which also appoints the elected members of the Foundation Council and the Board of Trustees. The Chairman of the Foundation Council of the Paul Ehrlich Foundation is Professor Dr. Thomas Boehm, Director of the Max Planck Institute for Immunobiology and Epigenetics in Freiburg, and the Chairman of the Board of Trustees is Professor Dr. Jochen Maas. Prof. Dr. Wilhelm Bender, in his capacity as Chairman of the Association of Friends and Supporters of Goethe University, is also a member of the Foundation Council of the Paul Ehrlich Foundation. The President of Goethe University is also a member of the Board of Trustees in this capacity.
– What is the significance of the cGAS-STING signaling pathway in the immune response?
Table of Contents
Three Renowned Scientists to Receive Prestigious Paul Ehrlich and Ludwig Darmstaedter Prize for Groundbreaking Discovery of cGAS-STING Signaling Pathway
The Paul Ehrlich Foundation has announced that Dr. Andrea Ablasser from the École polytechnique fédérale de Lausanne, Dr. Glen Barber from Ohio State University, and Dr. Zhijian ‘James’ Chen from the University of Texas Southwestern Medical Center in Dallas will be awarded the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize. This esteemed recognition is bestowed upon the trio for their pioneering discovery of the cGAS-STING signaling pathway, a critical alarm system that triggers the innate immune response when DNA enters the cell plasma.
Unraveling the Mysteries of the Innate Immune System
The presence of DNA in the cytoplasm of a cell poses a significant threat, whether it’s caused by viral invaders or cellular damage. The immune system must respond immediately to initiate defensive measures. The prize winners’ groundbreaking research, conducted between 2008 and 2013, has shed light on the intricate mechanisms of the innate immune system, revealing the crucial role of the cGAS-STING signaling pathway in detecting and responding to DNA threats.
A Century-Old Enigma Solved
In 1908, Ilya Mechnikov, a Nobel laureate in Medicine, reported that nucleic acids like DNA could trigger an immune reaction. However, the molecular biology underlying this response remained unclear for nearly a century. The discovery of the cGAS-STING signaling pathway by the prize winners has finally filled this knowledge gap.
The Breakthroughs
Dr. Glen Barber’s group identified the protein STING in 2008, which plays a pivotal role in directing the production of interferons in response to DNA viral infections. Dr. Zhijian ‘James’ Chen’s team then discovered the cyclic guanosine monophosphate adenosine monophosphate (cGAMP) molecule, a critical component of the cGAS-STING signaling pathway, in 2012. Dr. Andrea Ablasser characterized cGAMP in detail, demonstrating its distinct chemical properties and production mechanisms in 2013.
Understanding the cGAS-STING Signaling Pathway
The cGAS-STING signaling pathway is a complex system that enables the innate immune system to detect and respond to DNA threats. The enzyme cGAS acts as a sensor, binding to DNA in the cell plasma and triggering the production of cGAMP. This molecule, in turn, activates STING, leading to the production of interferons and other immune messengers that stimulate the formation of phagocytes and natural killer cells.
Implications for Human Health
The discovery of the cGAS-STING signaling pathway has far-reaching implications for the development of novel therapeutic strategies for treating infections, cancer, and inflammatory diseases. By understanding how the innate immune system responds to DNA threats, researchers can now explore new avenues for targeting these diseases more effectively.
A Landmark Achievement in Immunology
The Paul Ehrlich and Ludwig Darmstaedter Prize is a testament to the pioneering work of Dr. Andrea Ablasser, Dr. Glen Barber, and Dr. Zhijian ‘James’ Chen. Their groundbreaking research has opened up new possibilities for advancing our understanding of the innate immune system and has paved the way for the development of innovative treatments for various diseases.
Meta Description: Three renowned scientists, Dr. Andrea Ablasser, Dr. Glen Barber, and Dr. Zhijian ‘James’ Chen, will receive the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize for their groundbreaking discovery of the cGAS-STING signaling pathway, a critical alarm system that triggers the innate immune response.
Keywords: Paul Ehrlich and Ludwig Darmstaedter Prize, cGAS-STING signaling pathway, innate immune system, DNA, viral infections, cancer, inflammatory diseases, immunology, Dr. Andrea Ablasser, Dr. Glen Barber, Dr. Zhijian ‘James’ Chen.
What is the significance of the cGAS-STING signaling pathway in immune responses?
Breakthrough Discovery in Immunology: 2025 Paul Ehrlich and Ludwig Darmstaedter Prize Winners Unveiled
The Paul Ehrlich Foundation has announced the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize winners, recognizing the pioneering work of Dr. Andrea Ablasser from the École polytechnique fédérale de Lausanne, Dr. Glen Barber from Ohio State University, and Dr. Zhijian ‘James’ Chen from the University of Texas Southwestern Medical Center in Dallas. This prestigious award honors their groundbreaking discovery of the cGAS-STING signaling pathway, a crucial alarm system that alerts the immune system to the presence of DNA in the cytoplasm of cells.
The cGAS-STING Signaling Pathway: A Key to Understanding Immune Responses
The presence of DNA in the cytoplasm of a cell triggers a response from the immune system, which is essential for defending against viral invaders and cellular stress. The cGAS-STING signaling pathway is the molecular mechanism that enables this response. This intricate system involves a series of molecular signals that initiate an immune response, leading to the production of interferons and other immune messengers.
A Century of Discovery
Ilya Mechnikov, a Nobel laureate, first reported in 1908 that nucleic acids like DNA can trigger an immune reaction.