Cell-type specific tagging and tracing of metabolites in vivo

Key Facts

Speaker: Dr. Alex Gould
Employer and Department:
Francis Crick Institute
Location:
MSI-SLT
Date and Time:
Thu 26th Jun 2025 - 12:00

Abstract:

Stable isotope tracing is an important technique for studying metabolism but it has a major limitation. Isotope labelled metabolites have to be administered broadly from exogenous sources, such as the medium for cell culture or an injected/dietary bolus for animals. This makes it difficult to track metabolite transport from one specific cell or tissue type to another. A long-standing challenge in the field, therefore, has been to develop genetically-encoded methods to label metabolites within a specific cell type of a living animal. Here, we harness bioorthogonal reactions of selected xenoenzymes from microbes to add innocuous isotope or other tags to metabolites in a conditional cell-type specific manner. We establish that this methodology can be utilized to tag and trace fatty acids and branched-chain amino acids in vivo in Drosophila and in mice. The xenoenzyme approach is a powerful quantitative technology that enables the intercellular and interorgan exchange of metabolites to be analysed with unprecedented spatiotemporal resolution.

Bio:

Alex Gould FRS is a Principal Group Leader at the Francis Crick Institute in London. Research in his lab uses Drosophila and mouse models to understand how early-life environmental stresses affect the metabolism and physiology of the developing brain.

https://www.crick.ac.uk/research/labs/alex-gould