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Yeast as a tool to uncover the cellular targets of drugs
Christopher M Sturgeon1, Danielle Kemmer, Hilary J Anderson
1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Knowledge of the spectrum of cellular proteins targeted by experimental therapeutic agents would greatly facilitate drug development. However, identifying the targets of drugs is a daunting challenge. The yeast Saccharomyces cerevisiae is a valuable model organism for human diseases and pathways because it is genetically tractable and shares many functional homolog with humans. In yeast, it is possible to increase or decrease the expression level of essentially every gene and measure changes in drug sensitivity to uncover potential targets. It is also possible to infer mechanism of action from comparing the changes in mRNA expression elicited by drug treatment with those induced by gene deletions or by other drugs. Proteins that bind drugs directly can be identified using yeast protein chips. This review of the use of yeast for discovering targets of drugs discusses the advantages and drawbacks of each approach and how combining methods may reveal targets more efficiently.
Insights
Discovering drug targets is crucial for therapeutic development. This review explores using the yeast Saccharomyces cerevisiae and various methods, including gene expression analysis and protein chips, to efficiently identify drug targets.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Identifying cellular targets of therapeutic agents is essential for effective drug development.
- Drug target identification presents a significant challenge in pharmaceutical research.
Purpose of the Study:
- To review the utility of the yeast Saccharomyces cerevisiae as a model organism for drug target discovery.
- To discuss various methods for identifying drug targets in yeast and their comparative advantages and disadvantages.
Main Methods:
- Utilizing Saccharomyces cerevisiae's genetic tractability to alter gene expression and assess drug sensitivity.
- Inferring drug mechanisms of action by analyzing changes in mRNA expression profiles.
- Employing yeast protein chips to directly identify proteins that bind to therapeutic agents.
Main Results:
- Yeast offers a powerful platform for drug target identification due to conserved human pathways.
- Combining genetic manipulation, transcriptomic analysis, and protein-chip technologies can enhance target discovery efficiency.
Conclusions:
- Saccharomyces cerevisiae provides a versatile system for uncovering drug targets and elucidating mechanisms of action.
- Integrated approaches leveraging yeast's capabilities offer a promising strategy for accelerating drug development.
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