GPCR: problems and resolutions in hihg content screening

A review in the December, 2009 issue of Nature Methods, “GPCR: insane in the membrane” by Michael Eisenstein impressed me greatly. It presents a clear and wide view of the GPCR research fields, from the basic background knowledge, to difficulties and current solutions in real cases, to future development. After careful reading and thinking, I felt that there were still several questions left to for me to pounder.

1) The Plot Thickens

“In many cases, you identify a GPCR as a target based on physiological data, and the receptor might be expressed in the brain in a particular neuron, but then you perform a high-throughput screen in over expression, immortalized cell lines that are nothing like the cell in which the receptor normally resides,”This is the inherent problem for all the engineered and artificial cell based assays most widely used in GPCR research right now. As stated in this review, “There are so many ways to be misled by using an over-expressed receptor in a non-native cell line”, it was shocking to me, making me realize that cell line screening does not only have a problem of getting raw data of low quality, but also a problem of being seriously misleading, a problem of direction rather than efficiency.

Directed differentiation of iPS cells and ESCs might be one of the potential solutions to this problem. However, from our experience in iPS cells dedifferentiation and differentiation at Allele Biotech, as a main vendor of iPS cell reagents, it is hard to make this platform in current situation suitable for high content analysis of GPCR. As much as we wish and believe, like many other researchers and the general society, that stem cells will contribute significantly also to the drug screening field, much work needs to be done before that happens.

Primary cells could be a good alternative. Based on data from Allele Biotech’s trade partners in the primary cell business, the primary cells market has been expanding dramatically since late last year. I believe that the utility and advantage of primary cells have been increasingly appreciated. However, there are still some problems with using primary cells in GPCR studies. For example, neurons are hard to obtain and can not amplify in vitro, in which cases there seems to be no chance to satisfy the need by screening. In fact, neuron research is one of the main GPCR research fields. Therefore, this is a must-fix problem.

How about “Immortalized Primary Cells”? The immortalized primary cells maintain the properties of primary cells well, relative to established cell lines. We have built our own advanced immortalization technology, based on which new products and services will be released in the first season of next year. During the last several years, we have successfully immortalized immunological cells and cancer cells. WE have yet to have the experience of working with neurons. Anyone who has interests of cell immortalization is welcome to contact us for collaboration or custom service. “Introducing Cost Effectiveness to your research”, just as the slogan of Allele Biotech, we will be proud to serve you with cutting-edge technology and cost effectiveness!

2) Without a mark to be continued…

By Niels Yuhui Ni, researcher at Allelle Biotech

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Sunday, December 27th, 2009 Allele Mail Bag, iPSCs and other stem cells

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December 27, 2009

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