Group leader of bioinformatics and mathematical modelling
Affiliation:
Department of Molecular Systems Biology, University of Vienna, Austria
Email:
xiaoliang.sun@univie.ac.at
100-word biography:
Xiaoliang Sun obtained his bachelor and master degree in biomedical engineering from Southeast University, China, in 2001 and 2006 respectively, and PhD in bioinformatics from Max Planck Institute for Molecular Plant Physiology, Germany, in 2011. Since 2016 he has been core member of Vienna Metabolomics Center and since 2018 group leader in bioinformatics and mathematical learning in University of Vienna, Austria. He has developed statistics and mathematical modelling algorithms with multi-omics data, and pioneered in the inverse engineering of genome-scale omics data that lead to identifications of key regulatory points in the biochemical networks.
Title:
Inverse Data-Driven Modeling and Multiomics Analysis Reveals Phgdh as a Metabolic Checkpoint of Macrophage Polarization and Proliferation
Abstract:
Mechanistic or mammalian target of rapamycin complex 1 (mTORC1) is an important regulator of effector functions, proliferation, and cellular metabolism in macrophages. The biochemical processes that are controlled by mTORC1 are still being defined. Here, we demonstrate that integrative multi-omics in conjunction with a data-driven inverse modelling approach, identifies a biochemical node that influences overall metabolic profiles and reactions of mTORC1-dependent macrophage metabolism. Using a combined approach of metabolomics, proteomics, mRNA expression analysis, and enzymatic activity measurements, we demonstrate that Tsc2, a negative regulator of mTORC1 signaling, critically influences the cellular activity of macrophages by regulating the enzyme phosphoglycerate dehydrogenase (Phgdh) in an mTORC1-dependent manner. More generally, while lipopolysaccharide (LPS)-stimulated macrophages repress Phgdh activity, IL-4-stimulated macrophages increase the activity of the enzyme required for the expression of key anti-inflammatory molecules and macrophage proliferation. Thus, we identify Phgdh as a metabolic checkpoint of M2 macrophages.