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In
yeast studies, a mutated DNA reveals location, function of genes
Yale researchers
have discerned the functions of a third of the genes in the yeast
genome, using a novel method of DNA insertion that can be applied
to other organisms. The new tool will allow researchers not only
to identify genes, said principal investigator Michael Snyder,
Ph.D., but figure out what they do. “That is going to be
the next big challenge,” he said. Snyder and his interdisciplinary
team followed, using chemical markers, a mutated, bacterially
derived strain of DNA as it interacted with yeast genes and proteins.
They observed at what point in the yeast’s life cycle genes
were expressed, where in the cell proteins were located and what
disruptions the mutated DNA caused. Their results were published
in the Nov. 25 issue of the journal Nature. |
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Mitochondrial
voltage and neural connections
Mitochondria
are not only the energy packs of each living cell, but also judge
and jury, deciding whether cells live or die. Given that power,
aberrant mitochondria have long been suspects in degenerative
diseases such as Parkinson’s, in which cells die and crucial
neural connections are lost. The strength of those connections
depends on electrical activity in the mitochondria—the higher
the activity, the stronger the links. Now Yale researchers have
become the first to record electrical activity in the mitochondria
of living cells.
By inserting
microscopically thin glass pipettes into squid cells, which are
large and easy to manipulate, researcher Elizabeth A. Jonas,
M.D., was able to stimulate the nerve cells with electricity
for one or two seconds. Mitochondria in those cells seemed to
“remember” the stimulation for 30 seconds or more.
“Mitochondria have had less attention paid to them than
they deserve,” said principal investigator Leonard Kaczmarek,
Ph.D., professor of pharmacology. “We think they are very
important in determining the strength of the connections.”
The study was published in the journal Science on Nov.
12. |
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A
role for serotonin in
long-term memory
Yale scientists
have discovered a new mechanism for strengthening synapses that
store long-term memories. Applying the neurotransmitter serotonin
to pre-synaptic and post-synaptic cells in the sea slug Aplysia
strengthened the synapse if both cells received the serotonin
within 15 minutes of each other. Researchers had previously determined
that serotonin, which is linked to aggression and depression
in mammals, also would strengthen synapses when applied in sufficient
quantities to pre-synaptic cells. In the more recent experiments,
the researchers applied to both pre-synaptic and post-synaptic
cells amounts of serotonin too small to induce long-term memory
when applied to one cell alone. “It’s a new way of
signal processing within a cell that is different than what we
had thought of before,” said neurobiologist Carolyn Sherff,
Ph.D., a postdoctoral associate and co-author of the study with
Thomas Carew, Ph.D., professor of psychology and molecular, cellular
and developmental biology. Their study was published Sept. 17
in the journal Science. |
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At
last, a close-up view of the transcription process
In a discovery
that offers insights into fundamental cellular processes, Yale
researchers have observed for the first time the transcription
of genetic information from a DNA template to viral RNA. “In
general,” says Thomas A. Steitz, Ph.D., professor of molecular
biophysics and biochemistry, “the initiation of transcription
of DNA into RNA is one of the most heavily regulated steps in
cells. It is what makes one cell different from another.”
Steitz called the initiation events, observed through X-ray crystallography,
“scrunching.” The DNA, he said, coils like a rope inside
the enzyme polymerase, accumulating in the enzyme’s active
site as the first short RNA transcript is being synthesized.
The findings were published in the journal Science on
Dec. 17. |
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Shedding
light on Salmonella’s
Trojan Horse
To invade and
occupy a cell, Salmonella first deploys a Trojan horse,
a protein called SopE that instructs the cell to internalize
the bacterium. If left unchecked, however, this protein will
destroy the host and deny the Salmonella a safe haven from which
to replicate, penetrate deeper tissues and ward off attacks from
the immune system. Researchers in Yale’s Section of Microbial
Pathogenesis, who previously discovered a second Salmonella
protein, SptP, have now discerned its function. SptP protects
Salmonella’s new home by reversing the destructive
process started by SopE. “These findings bring us closer
to understanding the complex mechanisms by which these bacteria
cause disease and may lead to development of new therapeutic
and prevention strategies,” said Jorge E. Galan, Ph.D.,
who heads the section. The findings were published Sept. 16 in
the journal Nature.
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New
role found for B Cells in gastrointestinal disease
A team of Yale
researchers has traced a path of cellular development that may
lead to gastrointestinal and other ailments, including Creutzfeldt-Jakob
disease, which is related to mad cow disease. The trail starts
with the B cell, once thought capable only of producing serum
antibodies and activating T lymphocytes. Now researchers have
found that B cells are necessary for development of the M cell,
an intermediary between the body and organisms in the gut. Only
some of the M cell’s functions have been discerned. “M
cells play a role in sensitizing the immune system to gastrointestinal
flora,” said Mark Shlomchik, M.D., Ph.D., associate professor
of laboratory medicine and immunobiology, “but they are
also a portal of entry since many pathogens seem to enter the
body through M cells.” The work, done in collaboration with
a team at Jackson Labs, was published in the Dec. 2 issue of
the journal Science. |
