Regulation
of Cellular Excitablitly
Over the years, our research has been on the factors
that control the electrical excitability of nerve cells, particularly
ion channels. Ion channels are proteins that control the movement
of sodium, calcium and potassium through cell membranes, thereby
producing nerve spikes and other electrical events.
Recently we
broadened our focus somewhat and now work predominantly on the
factors that regulate the excitability of one of the most fascinating
cells in biology: the sting cells (cnidocytes) of jellyfish and
other cnidarians (jellyfish, sea anemones and corals). Since cnidocytes,
or sting cells, are arguably the most complex cells of any animal,
they are likely to be energetically very expensive for the animals
to produce. The investment the animal makes in producing these
cells is intensified by the fact that they can only be used once.
Not surprisingly, therefore, the discharge or firing of these cells
is tightly regulated to ensure that they do not discharge at the
wrong time. This work is being carried out using several jellyfish
species, most notably the Portugese Man of War, Physalia.
Current
Projects
The business end of a sting cell
is a large capsule (the cnidocyst) that occupies most of the volume
of the cell and envelops a tubule which, in nature, acts as a microscopic
hypodermic needle to inject toxin into the animal’s prey.
We are exploring the possibility of using sting cells as delivery
systems for therapeutic agents such as pharmaceuticals or antidotes.
We are working on a project that seeks, ultimately, to re-engineer
cnidocytes so that instead of injecting toxins, they inject drugs
or other chemicals of choice.
To achieve this goal we must understand
the pathways and mechanisms by which the toxins are normally produced
by the sting cell and then transported into the cnidocyst. The
best way to do this is to identify all the genes that are active
during the development and maturation of a cnidocyte. we are currently
using high-throughput DNA sequencing technologies to sequence genes
obtained from developing and mature cnidocytes. In addition, this
approach has the benefit of providing important information about
the synthesis and packaging of toxins. It will also provide a great
deal of other useful information; most notably identification of
all the toxins produced by the sting cells and a better understanding
of the various mechanisms used to regulate cnidocyte discharge.
At the same time, we are exploring
ways to isolate and culture interstitial cells, the stem cells
that differentiate into cnidocytes. These stem cells will then
be genetically re-engineered so that they synthesize and package
the drug of choice into the cnidocyst and, hence, be used as a
source of cnidocysts for microscale delivery devices.
Personnel
Peter
A. V. Anderson, Professor
Christelle Bouchard, Postdoctoral
Associate
Selected
Publications
Anderson, P.A.V. and Bouchad,
C.M. (In press) The regulation of cnidocyte discharge. Toxicon.
Price, R. B. and Anderson,
Peter A. V. (2006) Chemosensory pathways in the capitate tentacles
of the hydroid Cladonema. Invert. Neuroscience,6, 23-32.
Bouchard, C., Price, R. B., Money penny, C. G., Thompson, L. F.,
Zillhardt, M., Stalheim, L. and Anderson, Peter A. V. (2006) Cloning
and functional expression of voltage-gated ion channel subunits
from cnidocytes of the Portuguese Man O’War, Physalia physalis. J. Exp. Biol. 209, 2979-2989.
Kohn,
A.B., Roberts-Misterly, J.M.,
Anderson, P.A.V., Khan, N.,
and Greenberg, R.M. (2003).
Specific residues in the Beta
Interaction Domain of a schistosome
Ca2+ channel [beta] subunit
are key to its role in sensitivity
to the antischistosomal drug
praziquantel. Parasitology
127: 349-356.
Anderson, Peter A. V. (2004).
Cnidarian Neurobiology: what
does the future hold? Hydrobiologia,
in press.
Anderson, Peter A. V., Roberts-Misterly,
J. and Greenberg, R. M. (In
press) The evolution of voltage-gated
sodium channels: were algal
toxins involved? Harmful
Algae.
Kohn,
A.B., Anderson, P.A.V., Roberts-Misterly,
J.M., and Greenberg, R.M. (2002)
Schistosome calcium channel
ß subunits. Unusual modulatory
effects and potential role in
the action of the antischistosomal
drug praziquantel. J. Biol.
Chem. 276: 36873-36876.
Anderson,
Peter A. V. and Greenberg, R.M.
(2001). Phylogeny of Ion Channels:
Clues to Structure and Function.
Comp. Physiol. Biochem.
129B, 17-28.
Kohn,
A.B., Lea, J.M., Roberts-Misterly,
J.M., Anderson, P.A.V., and
Greenberg, R.M. (2001). Structure
of three high voltage-activated
calcium channel alpha1
subunits from Schistosoma
mansoni. Parasitology
124: 489-497.
Kohn,
A.B., Anderson, P.A.V., Roberts-Misterly,
J.M., and Greenberg, R.M. (2001).
Schistosome calcium channel
ß subunits. Unusual modulatory
effects and potential role in
the action of the antischistosomal
drug praziquantel. J. Biol.
Chem. 276: 36873-36876.
Jeziorski,
M.C., Greenberg, R.M. and Anderson,
Peter A. V. (2000). The molecular
biology of invertebrate voltage-gated
Ca2+ channels, J.
exp. Biol., 203: 841-856
Jeziorski,
M.C., Greenberg, R.M. and Anderson,
Peter A. V. (1999). Cloning
and expression of a jellyfish
calcium channel beta subunit
reveal functional conservation
of the alpha1 - beta
interaction. Receptors and
Channels, 6: 375-386.
White,
G.B, Pfahnl, A., Haddock, S.,
Lamers, S., Greenberg, R.M.
and Anderson, Peter A.V. (1998).
Structure of a Putative Sodium
Channel from the Sea Anemone
Aiptasia pallida.
Invert. Neurosci., 3:
317-326.
Jeziorski,
M.C., Greenberg, R.M., Clark,
K.S. and Anderson, Peter A.
V. (1998). Cloning and functional
expression of a voltage-gated
calcium channel alpha1
subunit from jellyfish. J.
Biol. Chem., 273: 22792-22799.
Blair,
K.L. and Anderson, Peter A.V.
(1996). Physiology and pharmacology
of turbellarian neuromuscular
systems. Parasitology
113: S73-S82.
Blair,
K.L. and Anderson, Peter A.V.
(1994). Physiology and pharmacology
of muscle cells isolated from
the flatworm Bdelloura candida.
Parasitology 109: 325-335.
Anderson,
Peter A.V., Holman, M. A. and
Greenberg, R.M. (1993). Deduced
amino acid structure of a putative
sodium channel from the scyphozoan
jellyfish Cyanea capillata.
Proc. Natl. Acad. Sci.
90: 7419-7423.
Blair,
K.L. and Anderson, Peter A.V.
(1993). Properties of voltage-activated
ionic currents in cells from
the brains of the triclad
flatworm Bdelloura candida.
J. exp. Biol. 185: 267-286.
Anderson,
Peter A.V., A. Moosler and C.J.P.
Grimmelikhuijzen (1992). The
distribution of AnthoRF-amide-like
immunoreactivity in scyphomedusae.
Cell Tiss Res. 267: 67-74.
Holman,
M. and Anderson, Peter A.V.
(1991). Voltage-activated ionic
currents in myoepithelial cells
from the sea anemone Calliactis
tricolor. J. exp. Biol.
161: 333-346.
Anderson,
Peter A.V. (1990). Evolution
of the First Nervous Systems,
Peter A. V. Anderson (Ed.).
Plenum Press, New York. 423p.
Anderson,
Peter A.V. and M. C. McKay (1987).
The electrophysiology of cnidocytes.
J. exp. Biol. 133: 215-230.
Anderson,
Peter A.V. (1987). Properties
and pharmacology of a TTX-insensitive
Na+ current in neurones
of the jellyfish Cyanea capillata.
J. exp. Biol. 133: 231-248. |