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Method to improve the yeast cell display

Yeast cells

Genetically modified cells of baker's yeast (Saccharomyces cerevisiae) synthesize proteins of interest on their cell walls using yeast surface display, a tool that enhances engineering and directed evolution of proteins. (Image: © M. Oeggerli/Micronaut , supported by University Hospital Basel and Biozentrum, University of Basel)

Researchers from the SNI network have developed a method to improve the so-called yeast surface display. Yeast surface display is a fundamental tool for protein engineering and targeted protein evolution.

In this process, yeast cells are equipped with specific genes encoding blueprints that instruct the cell how to build different versions of the protein on the surface of the cell that can interact and bind with other cells, proteins or antibodies. The binding then allows the researchers to select in an automated process the yeast cells on whose surface the desired proteins were anchored. 

The method is now widely used to select cells with a specific genetic makeup (genotype) using physiological characteristics (phenotype).

However, in the standard yeast surface display, the varying copy number of the displayed protein variants cannot be precisely controlled and this can complicate high-throughput screening experiments. A team led by Professor Michael Nash at the Department of Chemistry (University of Basel), the Department of Biosystems Science and Engineering (ETH Zurich) and the Swiss Nanoscience Institute has now developed a method to adjust protein copy numbers on yeast cells utilizing a genetic circuit in the scientific journal ACS Synthetic Biology.

"Using different model proteins, we have shown that by regulating the copy number of the proteins, we can influence specific phenotypic activities such as enzyme activity, cell attachment, or antibody binding," explains first author Joanan Lopez-Morales, a doctoral student at the SNI PhD School on Michael Nash's team. "The ability to influence biological properties on the yeast cell surface will benefit protein engineering and directed evolution for broad classes of therapeutic and diagnostic proteins," adds Michael Nash.

Original publication