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Technology: ORF-based functional screening


Ion channels mediate signaling within cells, between cells, and between cells and their environment. Defects in ion channels underlie many major disorders in humans, also known as “channelopathies”. Native ion channels often function as a complex of pore-forming subunits with its auxiliary or accessory subunits that modulate ion channel properties and pharmacology. Functional differences between native and recombinant ion channels can prove challenging when attempting to reconstruct native ion channel activity in heterologous cells for drug discovery. We have developed open-reading frames (ORFs) based high-throughput screening method to identify novel modulators for ion channels. Over the last two years we have focused to screen eight classes of ligand-gated ion channels with 4,000 transmembrane ORFs among total 19,000 distinct ORFs in human genome because transmembrane ORFs remain unexplored due to technical difficulties. In this phase I, we have identified novel modulators and some of modulators are previously classified as dark matter in the druggable genome. In conclusion, we have established a scalable ORF-based functional screening for ion channels, which could be expanded to genome-wide ORF-based screenings of various classes of ion channels to illuminate dark space of the druggable genome.


Genes Under investigation, Susumu Tomita, Ph.D.

Submitted 7/2/2016

Contact Susumu Tomita, Ph.D.

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