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i-HEAD

Immunometabolism in Health and Disease

Scientists in the Faculty of Medicine and the Faculty of Mathematics and Natural Sciences (MNF, Departments of Chemistry, Physics and Biology) at the University of Cologne (UoC) have teamed up with the Max Planck Institute for Plant Breeding Research (MPIPZ) and the MPI for Biology of Ageing to investigate the regulatory roles of metabolic signals and bioactive metabolites in immune systems.

The central goal of the interdisciplinary research consortium i-HEAD is to establish immunometabolism as an emerging field of research in host-microbe interactions. We hypothesize that immunometabolism is a fundamental property of immune systems across kingdoms of life that resulted in the evolution of potentially common and kingdom-specific infochemicals. In interactions with pathogenic microbes, such molecules connect host metabolism and immunity, underpin immune functions and regulate host metabolism. In beneficial interactions with microbes, metabolic signals integrate host and microbiota metabolic activities to establish metabolic homeostasis, which is critical for host health. We will broaden this emerging area of research in plant-microbe interactions by investigating unexplored extracellular and intracellular metabolic signaling mechanisms driving inflammation and disease in animal-microbe interactions.

Specific aims relate to:

  1. Emerging metabolic signals in immunity determining host-microbe interaction outcomes.
    • modulation of immunity by extracellular and intracellular nucleotide-based molecules and purinergic receptors
    • nucleotide-driven extracellular and intracellular calcium signaling and cyclic-nucleotide signal potentiation in host-microbe interactions
    • chemical synthesis and exploration of synthetic nucleotide-based prodrugs as immunostimulants for application in plant and animal disease resistance (e.g., pRib-ADP/AMP, ADP-ribosylated ATP, dAdo)
  2. Roles of infochemicals (signaling metabolites) underpinning interdependent metabolisms in beneficial host and microbe interactions, including the microbiota.
    • host and microbe-derived metabolite signals that drive metabolic interdependence in mutualistic host-microbe interactions
    • discovery and mode of action of stress-inducible infochemicals (e.g., 2’3’-cyclic nucleotides) in tuning host and microbe metabolism for stress adaptation, including malnutrition
    • metabolic signals as input of root-shoot axis circuits to maximize reproductive fitness of the host and its microbiota
  3. Evolution of immunometabolism in plants and animals driven by pathogens or beneficial microbial communities.
    • modelling of metabolic dependencies in resource competition and metabolic cross-feeding of host-microbe communities with photoautotrophic (plant) or heterotrophic (animal) hosts
    • evolvability and constraints of immunometabolism in photoautotrophic or heterotrophic hosts