Drug Testers Think Small...continued
Cellular Signaling
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GFP Tracks Proteins
into the Nucleus |
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GFP and its relatives are also good for seeing where proteins are in the cell. Some of the signals that tell a cell to grow either normally (as in wound repair) or aberrantly (as in cancer) exert their effect by sending a protein into the nucleus, the compartment of the cell that stores the DNA. Only in the nucleus can the protein switch on genes to get the cell growing. Attaching GFP to the protein doesn’t stop the protein from finding its way to the nucleus, but now it’s movement can be tracked.
About half of the technical staff at Aurora are engineers, a good indicator that machinery is as important as fluorophores. In about two years, Aurora aims to have its system fully operational, screening 100,000 compounds a day using 3456-well "nanoplates" that are the same size as conventional dishes that have 96 wells. Each well of a nanoplate only holds ~1 µl (10-6 liters, including tens to hundreds of cells). A pizoelectric device delivers volumes as small as 200 pl (where 1 pl is 10-12 liters) by using high frequency voltage pulses to create 2000 drops per second. The tiny volumes mean that chemicals can be delivered without the need for dilution beforehand.
In the meantime, Aurora is using prototype versions for the screening of ~10,000 single compounds a day, using 96-well and 384-well plates. Already the throughput is high enough to dispense with the complications of testing mixtures of several chemicals, which was done to cope with the flood of chemicals being made by combinatorial chemists. "Mixtures seemed like a good idea early on [in the history of combinatorial chemistry]," says Gordon Foulkes, until recently Aurora’s Chief Technical Officer. "But by the time you can screen as fast as we can, single compounds make a lot more sense."
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Biotech Revolutions Index
Biotech Applied Index
