Scientific concept
The immune sensory organ
Like a classical sensory system, the innate immune system possesses an elaborate receptor interface to sense and discriminate a large variety of stimuli. We like to view the innate immune system as an immune sensory organ with its diverse immune sensing receptors, since this term lives up to the capacity of the innate immune system to sense its environment.
Great advances have been made in the discipline of innate immunity, one of the most dynamic fields in life sciences. At the core of innate immunity lie pattern recognition receptors (here: immune sensing receptors), most of which have been discovered within the last twenty years. Immune sensing receptors detect foreign microbial molecules or altered self-molecules from tissue damage. The activation of immune sensing receptors initiates defense and repair mechanisms that normally protect the host. However, dysregulation of these responses can cause a range of inflammatory diseases. With the recent discoveries that particular immune sensing receptors are present in most somatic cells and that the metabolic state and neuronal inputs are tightly integrated, innate immunity has developed beyond the boundaries of classical immunology.
Immune Diversity
Still, our current understanding of the human immune system is an idealized one, where the immune system exists in only one prototypic form, best suited to maintain homeostasis and health. Any deviations from this normative immune system are perceived as non-ideal and inclined towards disease. But this view factors out a fundamental principle of immunology: immune diversity.
While this diversity may initially seem to be the trivial consequence of different genetic backgrounds and environments, immune diversity is the essential feature of the immune system at the population level. It ensures the survival of a population under constant environmental pressure and is hence a cornerstone of evolutionary fitness. However, disadvantages exist at the individual level, as certain combinations of genetic variants and environmental exposures can manifest as immune dysfunctions causing or contributing to diseases. Thus, immune diversity poses several scientific challenges, but also bears opportunities.
At ImmunoSensation3, we aim at understanding the genetic, the molecular and the functional mechanisms underlying immune diversity. We work on disentangling and characterizing the regulatory networks that maintain immune homeostasis under various genetic backgrounds and environmental exposures. We want to establish defined immunotypes and bio-markers to identify individuals at risk to develop specific diseases. And we aim to develop lifestyle and behavioral recommendations as well as tailored molecular tools for risk-adjusted prevention and treatment.
ImmunoSensation3 focusses on
- Identification of immune regulatory circuits governing immune homeostasis under
diverse genetic and environmental conditions - Assessment of immune diversity at scales from molecules to organisms
- Integration and harmonization of deep immunotype data and its reduction to applicable
biomarker panels for prediction, diagnosis and intervention - Application of advanced immune engineering to further basic research and translation
Research program
The scientific program of ImmunoSensation3 is designed to address key challenges in immunology, with an emphasis on immune diversity. While immune sensing is the common basis of all levels of an immune reaction and thus remains an important overarching topic of the scientific program, our goal now is to apply our current knowledge of the functional circuits that connect immune sensing, response, resolution, adaptation and memory, to immune diversity.
Immune diversity incorporates variations in the immune response at all scales resulting from genetic, epigenetic, environmental, lifestyle, aging, and other factors, and it is one of the decisive features of a robust immune defense at the population level. It is also reflected in defined immunotypes with important prognostic value. Unravelling immune diversity from molecules up to populations has great potential to improve risk prediction, prevent disease and enable tailored therapies. ImmunoSensation3 is determined to realize this translational potential.
Program 1: Immune Circuit Regulation
Program 2: Immunotypes
Program 3: Immune Intervention
Program 4: Advanced Approaches
Advanced collaborative research approach
All four programs together represent a truly collaborative approach of the applicants and the associated scientists, with every PI substantially contributing to more than one topic, and integrating additional contributing scientists as indicated, emphasizing the high degree of interdisciplinarity within the cluster. Moreover, within the different research areas of each program, tailored combinations of advanced collaborative approaches are used to address specific scientific questions.
To resolve the fundamental questions posed by the ImmunoSensation3 concept, the cluster relies on the unique and complementary expertise of its members and their collaborative access to advanced experimental designs.
The cluster has established a number of complementary scientific approaches since it last funding period, which are used to pertubate and characterize processes from the molecular level to entire organisms and multi-organism systems. Beyond the boundaries of classical immunology, the cluster encompasses expertise in related fields such as systems immunology and structural biology, and utilizes advanced tools and methods such as nanobody generation, Mass Spectrometry, protein crystallization, and more (see picture). These advanced scientific approaches will enable cluster members to design and adapt experimental settings which decode the specific regulatory immune circuits that are responsible for the functional connections between the level of immune sensing and the levels of response, resolution and memory.
The Cluster of Excellence addresses its concept by linking research on innate immunity at the University of Bonn with world-class expertise in neurobiology (German Center for Neurodegenerative Diseases, DZNE) and mathematics (Institute of Applied Mathematics). The University of Bonn, the Medical Faculty and the Life & Medical Sciences Institute (LIMES), have already established highly successful cross-faculty interactions, which have led to a number of important discoveries in the field of immune sensing, namely in inflammasome research, immunorecognition of nucleic acids, lectins and dendritic cells, local immune regulation in the liver and the gut, immune cell migration, the endocannabinoid system and the crossroad of metabolism and innate immunity. It is now evident that immune sensing is involved in many of the lifestyle-associated diseases of modern societies, such as atherosclerosis, metabolic syndrome and diabetes, neurodegeneration and cancer.
Achievements
The immune system is essential for our health, yet its dysregulation is involved in the pathogenesis of many common diseases. With the concept of an immune sensory system, which integrates the sensing functions of immune and non-immune cells, ImmunoSensation has become one of the leading centers for immunological research (Bonn Center of Immunology). Our seminal contributions, especially in the field of innate immunity, include the identification of novel receptor ligands, a new second messenger, new paradigms of cell-to-cell communication, a new classification of macrophage activation, insights into immunopathogenesis of cancer, a new target to restore cognitive function, and the impact of Western diet on trained immunity.
Read more in our final report from the first funding period
(2012 - 2018).
Prizes & Awards
ImmunoSensation3 brings together renowned scientists with internationally outstanding reputations. Accordingly, the members of the Cluster of Excellence include recipients of various prestigious prizes and awards.
Laureates of the Gottfried Wilhelm Leibniz-Prize
- Prof. Gunther Hartmann & Prof. Christian Kurts (2011)
- Prof. Frank Bradke (2016)
- Prof. Eicke Latz (2018)
ERC Grant holders
- Prof. Mihai Netea (ERC Consolidator Grant, 2012)
- Prof. Eicke Latz (ERC Consolidator Grant, 2013)
- Prof. Katrin Paeschke (ERC Starting Grant, 2015)
- Prof. Volker Busskamp (ERC Starting Grant, 2015)
- Prof. Bernardo Franklin (ERC Starting Grant, 2017)
- Prof. Elvira Mass (ERC Starting Grant, 2020)
- Prof. Carmen Ruiz de Almodóvar (ERC Consolidator Grant, 2020)
- Prof. Mihai Netea (ERC Advanced Grant, 2019)
- Prof. Martin Fuhrmann (ERC Starting Grant, 2020)
- Prof. Volker Busskamp (ERC Proof of Concept, 2021)
- Prof. Felix Meissner (ERC Consolidator Grant, 2023)
- Prof. Rayk Behrendt (ERC Consolidator Grant, 2022)
- Prof. Eicke Latz (ERC Advanced Grant, 2023)
- Prof. Rayk Behrendt (ERC Consolidator Grant, 2023)
- Dr. Lorenzo Bonaguro (ERC Starting Grant, 2024)
- Prof. Bernardo Franklin (ERC Proof of Concept, 2023)
- Prof. Jan Hasenauer (ERC Consolidator Grant, 2024)
- Prof. Matthias Geyer (ERC Advanced Grant, 2024)
- Prof. Florian Schmidt (ERC Consolidator Grant, 2024)
Emmy Noether Junior Research Groups
- Prof. Andreas Schlitzer (2015)
- Dr. Kerstin Ludwig (2016)
- Prof. Florian I. Schmidt (2017)
- Jun.-Prof. Tim Rollenske (2023)
Laurates of the Heinz Maier Leibnitz-Prize
- Prof. Natalija Novak (2005)
- Prof. Elvira Mass (2020)
NRW Return awards
- Prof. Christoph Wilhelm (2014)
- Prof. Eva Kiermaier (2017)
- Jun.-Prof. Dr. Swantje Liedmann (2022)