Dynamic metabolome profiling uncovers potential TOR signaling genes

Area of Science:

• Cellular Biology
• Systems Biology
• Metabolomics

Background:

• The function of many genes in Saccharomyces cerevisiae remains uncharacterized, hindering a comprehensive understanding of cellular biology.
• High-throughput metabolomics provides a powerful approach for functional genomics due to its cost-effectiveness, robustness, and broad applicability.

Purpose of the Study:

• To leverage dynamic metabolomics to identify novel genes involved in TOR signaling in Saccharomyces cerevisiae.
• To create a publicly accessible data resource for yeast TOR pathway research.

Main Methods:

• Dynamic metabolic profiling of 164 loss-of-function yeast mutants using flow-injection time-of-flight mass spectrometry.
• Time-course analysis of metabolite responses to rapamycin treatment.
• Development of an interactive data visualization application for exploring metabolomics data.

Main Results:

• Dynamic metabolite responses to rapamycin were more informative than steady-state responses for identifying known and novel TOR signaling regulators.
• Deletion of newly identified genes resulted in phenotypes and proteome changes implicating them in TOR signaling.
• The gene CFF1 was identified as a novel regulator connected to pyrimidine biosynthesis via URA10.

Conclusions:

• Dynamic functional metabolomics is effective for discovering novel genes associated with TOR signaling pathways.
• This study provides valuable insights into yeast cell biology and identifies new targets for further investigation within the TOR pathway.