A 2016 paper published by Vander Heiden Lab at MIT in collaboration with Elucidata highlighted the indisputable role of metabolic studies in identifying pathways and drug targets within lung tumors in mice. With the aid of LC-MS and GC-MS experiments using 13C glucose and 13C-glutamine feeds, the authors investigated nutrient utilization in TCA cycle of tumor cells in vivo and in vitro. The experiments revealed that environment determines the utilization of nutrients by tumor cells. The investigators found glutamine to be the main source of carbon for TCA in cells growing in-vitro whereas glucose oxidation was the primary source of carbon in-vivo.
Elucidata’s tools for processing, analysis, and visualization of labeling experiments (LC-MS, GC-MS, and LC-MS/MS) allow our partners to use similar approaches to study their biological systems of interest.
This 2015 paper was the result of a collaboration between researchers at Agios Pharmaceuticals and Washington University and was highlighted on the cover of the journal Immunity. The paper used a systems-level multi-omics approach to highlight metabolic and transcriptional changes that occur in macrophages during M1 and M2 polarization. The investigators combined mass spectrometry based metabolomic data with RNA-seq based transcriptional data in Combi-T analysis to make data-driven predictions about metabolic rewiring in macrophages. They validated their predictions using 13C labeling experiments as well as other targeted perturbation experiments.
We have since used similar multi-omics approach in many projects for comprehensive understanding of biological processes and to identify potential drug targets.