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Research Funding
02.06.2017

ERC Starting Grant for allergy research in the gut

The European Research Council (ERC) will be funding the ALLERGUT project at the Helmholtz Zentrum München for the next five years with an ERC Starting Grant. Working in this framework, the researchers headed by Dr. Caspar Ohnmacht want to discover if and how bacteria in the intestines can assist or prevent the development of allergies. The total funding amounts to 1.5 million euros.

ROR(γt)+ Tregs

ROR(γt)+ Tregs: Costained Foxp3 (nucleus in red) and ROR(γt) (reporter in cytoplasm, green) in the lamina propria of the large intestine. Source: Helmholtz Zentrum München

It is estimated that almost one out of three people in Europe suffers from one or more allergic diseases. Because the underlying mechanisms continue to be only superficially understood, current treatment forms can only alleviate the symptoms. The objective of the EU-funded ALLERGUT project is to explain why allergic reactions develop in the first place. As the name suggests, the search for allergy causes is focused primarily on the gut.

Project leader Caspar Ohnmacht and his team particularly want to take a close look at the interplay between the intestinal flora and the immune system. "The central element in our investigations will be the protein RORγt*," explains the head of the Mucosal Immunology Research Group at the Center of Allergy & Environment (ZAUM), Helmholtz Zentrum München and Technical University of Munich. He has spent years studying inflammatory processes that originate in the digestive system.

RORγt is a so-called transcription factor that, in the cell nucleus, can influence the expression of genes. Ohnmacht and his team have already been able to show that bacterial colonisation of the gut causes immune cells to produce RORγt there. As a result, immunological tolerance develops. This denotes the immune system's ability to distinguish its own structures and harmless foreign structures, such as gut bacteria or allergens, from pathogens and to tolerate their presence. RORγt particularly acts in the so-called regulatory T cells (Tregs) in the gut, which curb the immune system and ensure that excessive immune responses are avoided.

In the coming five years, Ohnmacht and his team want to examine a number of aspects in this regard. For instance, they want to determine what influence RORγt has on the development of allergy-triggering immune cells in the intestinal mucosa and also on other superficial organs. They are particularly interested in Treg-mediated tolerance.

“We are also going to study the question of which signalling pathways in the dendritic cells, which are cells that constantly monitor their environment, regulate the establishment of this type of tolerance,” explains Ohnmacht. The Helmholtz researchers would also like to clarify if there are certain bacterial or metabolic groups that support an allergic predisposition. “If we succeed here, it would be a giant step toward understanding why allergies and other chronic inflammatory diseases triggered by insufficient tolerance develop in the first place. This could make new preventive measures and the development of new treatment concepts possible in the future.”

Further Information

* The abbreviation stands for RAR-related orphan receptor gamma (RORγ). T indicates an (iso)form primarily found in the thymus.

Background:

The human body is inhabited by billions of symbiotic bacteria, carrying a diversity that is unique to each individual. The microbiota is involved in many mechanisms, including digestion, vitamin synthesis and host defense. It is well established that a loss of bacterial symbionts promotes the development of allergies. The Helmholtz-scientists have succeeded in explaining this phenomenon, and demonstrate how the microbiota acts on the balance of the immune system: the presence of microbes specifically blocks the immune cells responsible for triggering allergies.


The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.

The Institute of Allergy Research (IAF) investigates the molecular mechanisms behind the development of allergies, which are on the rise around the world. Through intensive cooperation among scientists and clinicians on individual approaches to prevention, the IAF is working to halt this epidemiological spread. In the therapeutic area, the institute's scientists want to develop new approaches specifically targeted at the patients. The IAF works with the Technische Universität München in the joint Center of Allergy & Environment (ZAUM) facility. The IAF is also a member of the Cluster Allergy and Immunity (CAI, www.cai-allergy.de) and the German Center for Lung Research (DZL).

Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 40,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, com-bined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany.