Ching Kung
Vilas Professor of Genetics and Molecular Biology
Ph.D., University of Pennsylvania, 1968
Postdoctoral Research: Indiana University and UCLA
National Academy of Sciences, 2011
American Academy of Microbiology Fellow, 2012
Lab Website: http://www.molbio.wisc.edu/kung/
Address: 321a Bock Labs
Telephone: 262-9472
E-mail: ckung@wisc.edu
Research Interests:
Microbial ion channels
Mechanosensitivity
Research Fields:
Neurogenetics
Microbial Genetics
Yeast and Fungi
Research Description: detail in web page http://www.molbio.wisc.edu/kung/
Our
laboratory studies microbial sensory transductions with emphasis on ion
channels. We have pioneered the
use of patch clamp on Paramecium, yeast, and E. coli, and continued to examine
microbial channel genes and proteins.
Current research is on the molecular biology and biophysics of eukaryotic mechanosensitive ion channels.
E. coli MscL: The mechanosensitive channel of large conductance was first detected
when we patch-clamped giant E. coli
spheroplasts. We then cloned and
dissected MscL while the Rees lab solved its crystal structure. MscL is now widely used as a tangible
molecular model for mechanosensations.
Prokaryotic K+ channels: The crystal structures of prokaryotic K+
channels by Mackinnon and others deepen our understanding on ion filtration and
channel gating. However, what
these channels do for any of these propkaryotes is entirely unknown! To find out, we have recently surveyed the
K+-channel genes in 270 prokaryotic genomes and are isolating and
studying mutants of Kch, the K+ channel of E. coli.
TRPY1: The yeast vacuolar membrane has a cation channel that
belongs to the TRP superfamily of sensory channels. It is mechanosensitive under patch clamp and can be
activated by osmotic upshock in vivo. Gain-of-function mutants with
exaggerated responses have been isolated and mapped.
Rat TRPV4: We have functionally expressed rat TRPV1 and TRPV4 in
yeast. One model in the literature
describes osmotic swelling to activate enzyme(s) generating ligands to open
TRPV4. Yeast has no such enzymes
or ligands. We have now expressed
rat TRPV4 in Xenopus oocyte and, by
patch-clamp examination, showed that it directly responds to membrane stretch
force. TRPV4 mutations have
recently been found to cause human disease in bone development and peripheral
neuropathy. We found one disease
allele to have spontaneous activity but have little change in
mechanosensitivity.
Paramecium: Ion channels govern its ciliary motion and therefore its
swimming behavior as in animals.
We have isolated behavioral mutants and some of the corresponding genes. The genome of this unicell has recently
been completely sequenced. It
contains 298 K+-channel genes! (Only 91 in human, 1 in budding
yeast, 1 in E. coli).
A
class of over-excitable mutants in Paramecium
have mutations at the C-lobe of calmodulin (CaM), while a class of
under-excitable mutants at the N-lobe.
We showed by patch clamp that CaM is a detachable subunit of a Ca2+-activated
channel. That CaM is often an
ion-channel subunit and has a functional bipartition have now been widely
observed among animal ion channels.
Representative Publications:
detail in web page http://www.molbio.wisc.edu/kung/
Loukin S, Su Z, Kung C (2011) Increased basal activity is
a key determinant in the severity of human skeletal dysplasia caused by TRPV4
mutations. PLoS ONE 6(5): e19533.
Kung, C., B. Martinac, and S. Sukharev (2010) Mechanosensitive channels in microbes. Annu. Rev. Miccrobiol. 64 313-329
Loukin, S., X.-L. Zhou, Z.-W. Su, Y. Saimi, and C. Kung
(2010) Wild-type and brachyolmia-causing
mutant TRPV4 channels respond directly
to stretch force. J. Biol. Chem. 285: 27176-27181
Su, Z.-W., et al. (2007) Yeast gain-of-function mutations
reveal structure-function relationships conserved among different subfamilies
of transient receptor potential channels. Proc. Natl. Acad. Sci. 104:
19607-1961.
Kung, C. (2005) A possible unifying principle for
mechanosensation. Nature. 436: 647-654.
Vilas Professor of Genetics and Molecular Biology
Ph.D., University of Pennsylvania, 1968
Postdoctoral Research: Indiana University and UCLA
National Academy of Sciences, 2011
American Academy of Microbiology Fellow, 2012
Address: 321a Bock Labs
Telephone: 262-9472
E-mail: ckung@wisc.edu
Research Interests:
Microbial ion channels
Mechanosensitivity
Research Fields:
Neurogenetics
Microbial Genetics
Yeast and Fungi
detail in web page http://www.molbio.wisc.edu/kung/
Our
laboratory studies microbial sensory transductions with emphasis on ion
channels. We have pioneered the
use of patch clamp on Paramecium, yeast, and E. coli, and continued to examine
microbial channel genes and proteins.
Current research is on the molecular biology and biophysics of eukaryotic mechanosensitive ion channels.
E. coli MscL: The mechanosensitive channel of large conductance was first detected
when we patch-clamped giant E. coli
spheroplasts. We then cloned and
dissected MscL while the Rees lab solved its crystal structure. MscL is now widely used as a tangible
molecular model for mechanosensations.
Prokaryotic K+ channels: The crystal structures of prokaryotic K+
channels by Mackinnon and others deepen our understanding on ion filtration and
channel gating. However, what
these channels do for any of these propkaryotes is entirely unknown! To find out, we have recently surveyed the
K+-channel genes in 270 prokaryotic genomes and are isolating and
studying mutants of Kch, the K+ channel of E. coli.
TRPY1: The yeast vacuolar membrane has a cation channel that
belongs to the TRP superfamily of sensory channels. It is mechanosensitive under patch clamp and can be
activated by osmotic upshock in vivo. Gain-of-function mutants with
exaggerated responses have been isolated and mapped.
Rat TRPV4: We have functionally expressed rat TRPV1 and TRPV4 in
yeast. One model in the literature
describes osmotic swelling to activate enzyme(s) generating ligands to open
TRPV4. Yeast has no such enzymes
or ligands. We have now expressed
rat TRPV4 in Xenopus oocyte and, by
patch-clamp examination, showed that it directly responds to membrane stretch
force. TRPV4 mutations have
recently been found to cause human disease in bone development and peripheral
neuropathy. We found one disease
allele to have spontaneous activity but have little change in
mechanosensitivity.
Paramecium: Ion channels govern its ciliary motion and therefore its
swimming behavior as in animals.
We have isolated behavioral mutants and some of the corresponding genes. The genome of this unicell has recently
been completely sequenced. It
contains 298 K+-channel genes! (Only 91 in human, 1 in budding
yeast, 1 in E. coli).
A
class of over-excitable mutants in Paramecium
have mutations at the C-lobe of calmodulin (CaM), while a class of
under-excitable mutants at the N-lobe.
We showed by patch clamp that CaM is a detachable subunit of a Ca2+-activated
channel. That CaM is often an
ion-channel subunit and has a functional bipartition have now been widely
observed among animal ion channels.
detail in web page http://www.molbio.wisc.edu/kung/
Loukin S, Su Z, Kung C (2011) Increased basal activity is
a key determinant in the severity of human skeletal dysplasia caused by TRPV4
mutations. PLoS ONE 6(5): e19533.
Kung, C., B. Martinac, and S. Sukharev (2010) Mechanosensitive channels in microbes. Annu. Rev. Miccrobiol. 64 313-329
Loukin, S., X.-L. Zhou, Z.-W. Su, Y. Saimi, and C. Kung
(2010) Wild-type and brachyolmia-causing
mutant TRPV4 channels respond directly
to stretch force. J. Biol. Chem. 285: 27176-27181
Su, Z.-W., et al. (2007) Yeast gain-of-function mutations reveal structure-function relationships conserved among different subfamilies of transient receptor potential channels. Proc. Natl. Acad. Sci. 104: 19607-1961.
Kung, C. (2005) A possible unifying principle for mechanosensation. Nature. 436: 647-654.
