kung ching

Dr. Kung studies the molecular basis of sensations. His lab pioneered the study of ion channels of E. coli, yeast, and Paramecium, instead of animals, to take advantage of the genetics of these model microbes.

Patch clamp revealed mechanosensitive ion channels in E. coli. MscL was cloned, mutated, and later crystalized by the Rees lab. It is now the key biophysical model of molecular mechanosensitivity. A key lesson is that the force that opens these channels comes from the lipid bilayer, as incontrovertibly demonstrated by reconstituting purified MscL into bilayers of defined lipids. This concept is being extended to eukaryotic channels.

Budding yeast has several ion channels, including the mechanosensitive TRPY1 channel. Gain-of-function mutations showed that TRPY1 and animal TRPs have similar submolecular arrangements. Peptide-insertion experiments showed that stretch force opens TRPY1 likely by directly pulling on the channel core instead of the peripheral domains.

Paramecium behavioral genetics shows that channel mutations can erase or lengthen action potentials. Surprisingly, a set of over-reactors is mutated in the C-lobe of calmodulin while under-reactors in the N-lobe. Patch clamping shows that calmodulin is a detachable subunit of the Ca2+-dependent channels involved. Calmodulin functional bipartition and its regulation of channels are now widely observed.