Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cellular insights via barcoded yeast genes

22.06.2009
A newly created yeast gene archive will enable efficient analysis of the function of bioactive compounds with potential pharmaceutical use

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

Saeko Okada | Research asia research news
Further information:
http://www.rikenresearch.riken.jp/research/725/
http://www.researchsea.com

More articles from Life Sciences:

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

NASA examines Peru's deadly rainfall

24.03.2017 | Earth Sciences

What does congenital Zika syndrome look like?

24.03.2017 | Health and Medicine

Steep rise of the Bernese Alps

24.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>