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SFB 1454:  Metaflammation and Cellular Programming

Subject Area Medicine
Biology
Term since 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 432325352
 
Evolutionary constraints have selected humans for sensitive and effective anti-microbial immune responses, energy efficiency and storage, and elevation of blood glucose levels during inactivity or infection. These traits provided increased fitness in times in which constant pathogenic threats and periods of starvation were common. The human environment in the developed world, however, has drastically changed. While infectious triggers of the immune system have diminished, non-infectious immune and metabolic triggers from Western-type diets, man-made bioactive substances, pollution, or smoking, now pose a significant risk to human health. The overabundance of food paired with sedentary behaviours has, furthermore, led to an unprecedented increase in positive energy balance. Therefore, the evolutionarily favoured immune and metabolic adaptations have become a liability for modern humans. Immunometabolic diseases, including obesity, type II diabetes, cancer, asthma, and neurodegeneration, are on the rise, and some of these diseases have reached epidemic proportions. Research in the last decades has revealed that the immune and metabolic systems respond to a modern lifestyle with chronic, low-grade inflammation, which is called metaflammation, and is causally linked to the development of many non-communicable diseases (NCD).The CRC brings together the transdisciplinary expertise from three faculties of the University of Bonn (Medicine, Mathematics and Natural Sciences, and Philosophy), the German Center for Neurodegenerative Diseases, the Max-Planck-Institute for Metabolism Research in Cologne, and the Braunschweig Integrated Centre of Systems Biology to collaboratively address the unmet need to understand the mechanisms leading to metaflammation and to translate these findings into novel therapeutic and preventative strategies. The CRC aims to i. study how the triggers associated with a Western lifestyle lead to immune cell programming and cause metaflammation, ii. investigate the crosstalk between reprogrammed immune cells and the inflamed tissues, iii. address the role of specific pathways activated in metaflammation for disease pathogenesis, iv. perform bi-directional translational research between murine and human studies by investigating the discovered mechanisms in patient populations as well as in the longitudinal population ‘Rhineland Study’. A particular strength of the CRC is a systems immunology approach that uses unbiased multi-omics investigations combined with sophisticated bioinformatics analyses to decipher the causes and consequences of metaflammation. This work will provide a more holistic understanding of how metaflammation and cellular programming trigger the development of organ pathology and dysfunction and will reveal new targets for pharmacological intervention and generate the necessary evidence to foster the initiation of effective preventative strategies.
DFG Programme Collaborative Research Centres

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Participating University Technische Universität Braunschweig
 
 

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