I saw this article on the Scientific American website.

http://www.sciam.com/article.cfm?chanID=sa004&articleID=0006ED18-FBC3...

Here is the text of the article.

July 03, 2006
BIOLOGY

An Immune Portal
Protein may be a key to autoimmune disorders
By Jeneen Interlandi

As a medical student in Germany, Stefan Feske studied two Turkish
brothers born with severe combined immunodeficiency syndrome, or SCIDS,

a rare, life-threatening genetic disease characterized by a seriously
debilitated immune system. Because the boys' T cells could not take up
calcium, their immune systems would not work. These siblings provided
Feske and his collaborators with a unique opportunity to track down a
key protein involved in this process by studying human cells in which
it was already dysfunctional. "You cannot do this for every gene hunt,"

says Feske, now an assistant professor of pediatrics at Harvard Medical

School.

That search ended recently with the discovery by Feske and his Harvard
collaborators, Anjana Rao and Yousang Gwack, of Orai 1, a protein that
may be part of the ion channel that admits calcium into T cells, a step

required to set the body's immune response in motion. The group's
endeavors, reported in the May 11 issue of Nature, represent several
years of investigations that were part of a larger 20-year effort to
track down this critical cog in immune functioning.

Because the pathway that this channel participates in has been
conserved throughout evolution, fruit flies and humans still make and
use many of the proteins involved in much the same way. Recognizing
this similarity, Gwack, now a research associate in pathology at
Harvard, developed a genetic screen in fruit flies that complemented
Feske's patient studies. By expressing a key human protein in fruit fly

cells, Gwack was able to search for the elusive calcium channel in the
fly's smaller genome. His data, combined with a genetic analysis of the

siblings' extended family, led the team to a single gene that was
mutated in both patients. Gwack named the new protein encoded by the
gene Orai 1, after the keeper of heaven's gate in Greek mythology.

Ion channels facilitate the movement of specific molecules, such as
calcium or potassium, into and out of cells. Because these proteins
span the cell membrane, they make a particularly appealing target for
finding new drugs. "The problem for most drugs is that they have to get

into the cell," Feske says. Getting into a cell means getting past its
membrane, something ion channels were made to accomplish.

Drug companies around the world have been searching for ion channels
specific to the immune system, especially a particular calcium channel,

whose genetic identity has evaded researchers for two decades. The
discovery of Orai 1, which may be a subunit of the immune system's
calcium channel, represents a major breakthrough in that initiative.
"The impact is going to be huge," says Michael Xie, director of
ion-channel research at Synta Pharmaceuticals in Lexington, Mass.,
which is developing drugs that interact with this calcium channel.
"Inhibition of this immune channel could provide one of the most direct

means of manipulating the immune response."
Because drugs that block this passageway would stifle the body's immune

response, they could be useful in treating a variety of autoimmune
disorders, such as allergies and rheumatoid arthritis, which occur when

the body's immune system turns against itself. Scientists also hope
further research on Orai 1 will lead to better drugs for preventing
transplant rejection, which occurs when the immune system attacks a
donor organ. Drugs that home in on this apparently immune-specific
calcium channel could avoid side effects, such as kidney impairment and

neurotoxicity, caused by other transplant drugs, which interact with
molecules found in several types of cells.
Still, more work remains before scientists can be certain of the role
that Orai 1 plays. It is possible, for example, that the newly
discovered protein is not a component of the channel itself but rather
a modulator, or key, that opens and closes the channel like a doorway.
And even if Orai 1 turns out to be a channel protein, it may be only
one of the components that makes up the channel. "It's not the end of
the story," Gwack says. "But the whole field is getting very, very hot
now."