Recent discoveries put metabolism into spotlight. Metabolism not only fuels cells, but also plays key roles in health and disease, in particular in cancer, inflammation, and immunity. In parallel, emerging single-cell technologies opened a new world of heterogeneous cell types and states previously hidden beneath population averages. Yet, methods for discovering links between metabolism, cell states, metabolic plasticity and reprogramming on the single-cell level and in situ are crucially lacking.

Our research aims to bridge this gap. First, I will explain how the emerging technology of imaging mass spectrometry can be used for spatial profiling of metabolites, lipids, and drugs in tissues. I will present our cloud and Artificial Intelligence-powered platform METASPACE which is increasingly used across the world. 

In the second part of my talk I will focus on our method SpaceM for spatial single-cell metabolomics in situ. We applied SpaceM to investigate hepatocytes stimulated with fatty acids and cytokines, a model mimicking the inflammation-associated transition from the fatty liver disease NAFLD to steatohepatitis NASH. We characterized the metabolic state of steatotic hepatocytes and metabolic plasticity associated with the inflammation. We discovered that steatosis and proliferation take place in distinct cell subpopulations, each with characteristic spatial organization and metabolic signatures. 

Overall, such methods open novel avenues for understanding metabolism in tissues and cell cultures on the single-cell level.

Professor Theodore Alexandrov

Professor Theodore Alexandrov.

Theodore Alexandrov is a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, the head of the EMBL Metabolomics Core Facility and an Assistant Adjunct Professor at the Skaggs School of Pharmacy, University of California San Diego. 

The Alexandrov team at EMBL aims to reveal secrets of metabolism in time and space in tissues and single cells by developing experimental and computational methods. The team unites interdisciplinary scientists from biology, chemistry, and computer science as well as software and machine learning engineers. 

Theodore Alexandrov is a grantee of an ERC Consolidator project focused on studying metabolism in single cells, as well as of various other European, national, NIH, and industrially-funded projects. He has co-founded and scientifically directed the company SCiLS and has over 70 journal publications and patents in the field of spatial -omics.

Seminar host: Professor Ian Henderson

About IMB Friday Seminar