Inside Salk - October 2008 - page 7

Marc Montminy,
professor of the Clayton
Foundation Laboratories for Peptide
Biology, who is interested in deeper
research of protein-DNA interaction.
Also, the same technique Ecker’s
lab developed to pinpoint bacterial
T-DNA insertions in Arabidopsis has
been applied in a collaborative study
to look at integration of the HIV/AIDS
virus into the human genome.
“The biology that’s carried out by plants
can have a direct impact on understanding
human biology because genes are genes,
proteins are proteins,” Ecker says. “If I can
understand the function of a particular
molecular transporter in plants, for
example, it probably does the same thing
in humans.”
standard trick to determine their function.
“What we’ll be able to start to see is an
interconnection of the biology that youmight
not ever test if your particular lab only works
on [response to] light,” Ecker explains. “But
if you can see that someone else found that
the mutation affects another process, then
you can say, ‘I found a new connection.’ The
idea is to integrate the biology through the
gene networks.”
A valuable and highly used resource for
gene testing is readily available through the
Salk Institute’s Genomic Analysis Laboratory,
which preserves a massive collection of
Arabidopsis gene mutations, copies of which
are used for research worldwide.
Just steps away from Ecker’s office is the
temperature-controlled room that houses what
is perhaps the world’s largest bank of
Arabidopsis seeds that represent 400,000
insertions, or points on the genome where
bacterial “transfer-DNA,” or T-DNA, entered
and caused a unique gene mutation.
Ecker developed the sophisticated
technique that enables his lab to identify the
exact location of each insertion point. In
2003, Science published the revolutionary
study, which has since been citedmore than
1,100 times and is ranked No. 14 among
ISI’s highly cited, “Super Hot” papers.
“The plant biology world knows Salk
because the Institute is linked to these
seeds,” Ecker says. “But again, by using
Arabidopsis as the reference plant, the
functions of its genes can be determined by
studying their mutations. By having a
complete genetic guide to Arabidopsis, we
can then apply that knowledge to other plants
like soybean or wheat.”
Of course, being able to develop a genetic
reference book for Arabidopsis assumes that
the structures and functions of all the genes
in the genome are known. But this isn’t the
case, Ecker says. Although plant biologists
now have the genome, Ecker estimates that
the exact structures for many of the genes are
still waiting to be discovered.
How is this possible? Some genes are
expressed at very low levels and their signals
can’t always be detected. To hunt them down,
Ecker’s lab developed powerful high-
throughput DNA sequencing technology.
The new-generation sequencing machine
maps the precise location of the missing
genes by isolating their byproduct: RNA.
“By performing a deep sequencing of the
transcriptome, we’re asking the genome to
tell us, ‘Where are your genes?’ ” Ecker says.
This is an ongoing project in his lab, but
others in the scientific community have taken
notice of this new tool.
Applications to Human Biology
Ecker’s sequencing technology, for
example, is now being applied to understand
the dynamics of the human genome, and is
providing greater insight into human stem
cells’ capacity to self-renew and how other
sub-DNAmolecules contribute to the
development of tumors and disease.
This has led to additional interdisciplinary
collaborations at Salk between Ecker’s
lab and
Fred H. Gage,
professor of
the Laboratory of Genetics, and
7
Inside Salk October 2008
COVER STORY
Using Arabidopsis as the reference
plant, the functions of its genes can
be determined by studying their
mutations. By having a complete
genetic guide to Arabidopsis, we can
then apply that knowledge to other
plants like soybean or wheat.
– JOE ECKER
JimUmen
The Genomic Analysis Laboratory’smassive collection of Arabidopsis seeds.
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