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Our laboratory studies sensory transductions in microbes. We have pioneered the study of ion channels in Paramecium, yeast, and E. coli. The powerful microbial genetics is used to dissect the basic working of ion channels and to define their physiological roles.
We found the activity and cloned the gene for a mechanosensitive channel, MscL of E. coli. This channel, homopentameric in crystal, protects the bacteria from lysis upon osmotic downshocks. MscL shows definitively that channels receive forces from the lipid bilayer. This fundamental concept is being extended to eukaryotic channels.
We also study the K+ channels of bacteria and yeasts. Forward and reverse genetics are used to dissect this molecule. Similarly we discovered and continue to study a cation channel of the TRP family on the vacuolar membrane of yeast.
The motile behavior of Parameicum is governed by its excitable membrane. Behavioral mutants were isolated and genes cloned. They predict ion exchangers or channel regulators. Two classes of mutants led to the insight that the universal Ca2+ transducer, calmodulin, is often an ion-channel subunit and has a funtional bipartition. These concepts have now been extended to a large number of animal ion channels.
Forward genetics plays a central role in our studies of microbiol ion channels. The use of "gain-of-function" mutations that yield "loose-cannon" channels is especially powerful.