B-ACTIVE · Training of young scientists in the Biological regulation of the chemokine network to improve treatment of ACTIVE inflammation

A number of pharmaceuticals targeting cytokine/chemokine storms in lungs are in development due to an urgent new unmet medical need strengthened by the COVID-19 pandemic. The recent death of > 6.5 million people shows that treating excessive inflammation is still a major problem. Our incomplete understanding of complex immune reactions and resulting doubts on correct drug target identification prohibit efficient drug development and patient treatment. Proper control of inflammation is crucial during infection, wound healing, auto-inflammation, auto-immunity, transplant rejection, etc. Chemokines and their receptors drive leukocyte migration and activation and inflammation. Although the ligands and receptors were identified in the last 3 decades, increasing fundamental, preclinical and sporadic clinical evidence indicates that posttranslational regulation of chemokine ligands and receptors may impact the inflammatory reaction significantly. In this B-ACTIVE network, fundamental and clinical scientists and companies will study the impact of posttranslational modifications of chemokine ligands and receptors and train 10 early stage researchers (ESRs) to future experts in this domain with a translational and interdisciplinary mindset and a network founded already in graduate education. The ESRs will characterize interactions between ligands, receptors and glycosaminoglycans, study signaling pathways and recognize their importance in inflammatory reactions. ESRs will be trained in the complexity of inflammatory responses from basic science to clinical applications and industrial development. B-ACTIVE will improve our understanding of inflammatory reactions, aid in identifying the right drug targets and participate in pharmaceutical development, for better patient treatment with more new active pharmaceutical ingredients being evaluated clinically. The proposed projects are aligned with this overall objective and research strategies of academic and industrial partners.