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Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae
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Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome.

Yuko Arita1, Shinichi Nishimura, Akihisa Matsuyama

  • 1Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.

Molecular Biosystems
|February 23, 2011
PubMed
Summary
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Researchers developed a new microarray system to quickly identify the cellular targets of small molecules. This method uses drug-hypersensitive yeast strains to find drug targets and pathways, accelerating drug discovery.

Area of Science:

  • Molecular Biology
  • Genomics
  • Drug Discovery

Background:

  • Identifying the cellular targets of small molecules is crucial for developing new drugs and biological tools.
  • Current methods for target identification can be time-consuming and require large amounts of compound.
  • A need exists for efficient, genome-wide screening methods for small molecule target identification.

Purpose of the Study:

  • To develop and validate a novel microarray-based system for the high-throughput identification of small molecule targets and pathways.
  • To demonstrate the utility of this system using etoposide as a model compound.
  • To accelerate the process of target identification for drug leads and biological probes.

Main Methods:

  • A microarray system was created using a collection of drug-hypersensitive fission yeast strains, each overexpressing a specific gene from the open reading frame-ome.

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  • This system allows for genome-wide screening of small molecule sensitivity.
  • The method requires a relatively small amount of the test compound for screening.

    • Main Results:

    • The system successfully identified 28 genes associated with etoposide sensitivity.
    • These identified genes include the known drug target, topoisomerase II, as well as other genes involved in etoposide tolerance.
    • The results demonstrate the system's capability for accurate and efficient target identification.

    Conclusions:

    • The novel microarray-based system provides an efficient and cost-effective approach for identifying small molecule targets and pathways.
    • This method accelerates the drug discovery pipeline by enabling rapid target validation.
    • The approach has the potential to uncover conserved genes with significant clinical relevance.