Biological Sciences
Molecular Biology
To study the biological effect of a new compound on signal transduction pathways, the target must first be validated.
One approach taken by the Molecular Biology group here at Merck Frosst, is to clone all possible proteins related to a target, such as a receptor, and then express the clones in a mammalian or eukaryotic cell line.
In cells over-expressing the specific target gene, changes can be visually monitored and measured using leading-edge technology such as confocal microscopy. These biochemical changes also serve as markers of drug activity. Automated cell-based assays speed the process of drug screening.
An alternative approach to target validation by the Molecular Biology group is the development of transgenic animal lines. Researchers at Merck Frosst assess the potentially beneficial effects of blocking the function of a protein target, by creating a mouse line that lacks the gene of interest. This approach was used in a study published in Science in 1999, where the molecular biology team knocked out an interesting tyrosine phosphatase. The phenotype of the resulting mouse strain confirmed that this enzyme was a promising target for potential drugs to treat type 2 diabetes and obesity.
One approach taken by the Molecular Biology group here at Merck Frosst, is to clone all possible proteins related to a target, such as a receptor, and then express the clones in a mammalian or eukaryotic cell line.
In cells over-expressing the specific target gene, changes can be visually monitored and measured using leading-edge technology such as confocal microscopy. These biochemical changes also serve as markers of drug activity. Automated cell-based assays speed the process of drug screening.
An alternative approach to target validation by the Molecular Biology group is the development of transgenic animal lines. Researchers at Merck Frosst assess the potentially beneficial effects of blocking the function of a protein target, by creating a mouse line that lacks the gene of interest. This approach was used in a study published in Science in 1999, where the molecular biology team knocked out an interesting tyrosine phosphatase. The phenotype of the resulting mouse strain confirmed that this enzyme was a promising target for potential drugs to treat type 2 diabetes and obesity.
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