Physiological regulation of metabolism in single cells

Theo Alexandrov (EMBL) & Katrin Svensson (Stanford)

Background

The molecular compounds taken in from the environment are used in all aspects of cellular life: to produce energy, as basic substrates for protein assembly, and as essential cofactors for metabolic processes. The essential pathways behind energy metabolism–glycolysis, the TCA cycle, oxidative phosphorylation–are highly conserved across all eukaryotic organisms and are essential to nearly all cellular processes. However, these metabolic processes are dysregulated in many age-related diseases, in part due to impaired intercellular crosstalk and signaling. As dysregulated metabolism is implicated in driving aging, obesity, diabetes, and neurodegenerative diseases, a better understanding of the underlying mechanisms is necessary to develop new treatments.

Project

Combining single-cell metabolomics and secretomics approaches to identify mechanisms of metabolic regulation

By using a combination of computations, transcriptomics, and proteomics approaches, the Svensson lab at Stanford has discovered new functions for secreted signaling polypeptide factors in regulating nutrient uptake and organismal metabolism.  The overall aims of this research are to utilize advanced single-cell metabolomics approaches developed in the Alexandrov team at EMBL Heidelberg to examine the metabolic, spatial, and phenotypic characterization of cells in response to these novel polypeptide factors. This project therefore combines these interdisciplinary approaches in spatial single-cell metabolomics (Alexandrov team, EMBL Heidelberg) with secretomics and functional approaches (Svensson lab, Stanford) to identify mechanisms of hormonal control of metabolism.

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