Cellular insights via barcoded yeast genes

By establishing a library of individual yeast genes, each cleverly tagged with its own molecular barcode, an international team of molecular geneticists has designed a valuable resource for pharmaceutical research with advantages over previous approaches.

The research team, including Minoru Yoshida at the RIKEN Advanced Science Institute in Wako, and Charles Boone at the University of Toronto, Canada, developed the library in which each yeast gene is copied and attached to two unique single stranded DNA molecules that act as barcodes. This enables researchers to efficiently identify each gene.

The yeast-based chemical-genomics approach, presented recently in Nature Biotechnology by Yoshida and colleagues (1), is useful because many medicinally important drugs target fundamental biological processes that are conserved between yeast cells and higher organisms.

Using the team’s approach, all the gene-carrying units, or plasmids, in the yeast are carefully constructed individually, as opposed to conventional genomic libraries that are created from random fragments of DNA. Each plasmid carries a single yeast gene as well as two 20-nucleotide barcodes that identify it. The library comprises plasmids for almost 5,000 genes and covers approximately 90% of the yeast genome.

Other approaches to examine the genetic influence of potential drugs have limitations such as needing high volumes of test compound, which can be of limited availability, or being labor intensive.

Most significantly, the newly created gene catalogue will enable researchers to identify at the genetic level the precise modes of action of specific compounds that are being screened as potential pharmaceuticals. The library can be used to efficiently identify mutant genes that confer resistance to a test drug by comparing cells that show resistance and susceptibility to the compound. Determination of the mutant genes leads to the identification of the functional impact of a potential drug.

In a demonstration of the usefulness of the library, Yoshida and colleagues identified the gene responsible for conferring resistance to a novel class of compounds with pharmaceutical potential. Identifying this gene enabled the team to characterize the mechanism of action of these molecules and to determine that they are antifungal compounds, a property not detected by other techniques.

An essential but challenging step in the development of small molecules into therapeutic drugs is identification of their cellular target. “Using this library, our group intends systematically to study chemical–genetic interactions in which an altered gene dosage or gene mutation leads to a change in cellular response to a bioactive compound,” says Yoshida.

Ho, C.H., Magtanong, L., Barker, S.L., Gresham, D., Nishimura, S., Natarajan, P., Koh, J.L.Y., Porter, J., Gray, C.A., Andersen, R.J. et al. A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds. Nature Biotechnology 27, 369–377 (2009).

The corresponding author for this highlight is based at the RIKEN Chemical Biology Department, Chemical Genomics Research Group

Media Contact

Saeko Okada Research asia research news

Alle Nachrichten aus der Kategorie: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Zurück zur Startseite

Kommentare (0)

Schreib Kommentar

Neueste Beiträge

Cyanobacteria: Small Candidates …

… as Great Hopes for Medicine and Biotechnology In the coming years, scientists at the Chair of Technical Biochemistry at TU Dresden will work on the genomic investigation of previously…

Do the twist: Making two-dimensional quantum materials using curved surfaces

Scientists at the University of Wisconsin-Madison have discovered a way to control the growth of twisting, microscopic spirals of materials just one atom thick. The continuously twisting stacks of two-dimensional…

Big-hearted corvids

Social life as a driving factor of birds’ generosity. Ravens, crows, magpies and their relatives are known for their exceptional intelligence, which allows them to solve complex problems, use tools…

By continuing to use the site, you agree to the use of cookies. more information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close