In this sub-project, we aim to characterize different human intestinal macrophage populations and their metabolic signatures at single cell level in situ to depict cellular metabolic heterogeneity. We recently developed a first approach to profile central carbohydrate metabolism in single cells in situ. With this novel tool we will significantly contribute to the goal of this consortium by exploring the immunometabolic profile of macrophage populations in vivo. Using a multimodal imaging approach, we will establish the metabolic signatures of macrophages and of their neighboring cells in situ by assessing key cellular enzyme activities driving glycolysis, the pentose phosphate pathway and TCA cycle in antibody-defined single cells. We will investigate the metabolic signatures of different human macrophage populations and other tissue-resident cells in healthy and diseased tissue biopsies of patients. We will evaluate in situ findings by testing targeted metabolic interventions and their functional consequences in human tissue culture and organoids was well as in animal disease models (E. Pohl, G. Egger, T. Weichhart) for identification of immunometabolic targets in human diseases. We will compare our data to adipose tissue macrophages and depict associations with the microbiome (M. Schweiger, G. Schabbauer, C. Moissl-Eichinger). We expect that metabolic profiling of human macrophages within their physiological and pathophysiological microenvironments by multimodal analysis will provide a better understanding of their tissue heterogeneity and indicate novel therapeutic opportunities or guide clinical decision making in precision medicine.

Nikolina Bradarić
PhD Student

SFB member

Chuqiao Chen
PhD Student
SFB affiliated