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One possible research direction involves the counter-regulation
of the primary, inflammatory responses to the viral infection.
The body naturally makes substances that counter this process,
and Sarvetnick is interested in elucidating both what these
factors are and how they work.
Another direction is to study the regulation of the acquired
immune cell response. Killer T cells are responsible for the
immune reaction that leads to the onset of diabetes, and these
are regulated in the body by cytokine molecules. Cytokines
are produced by pancreatic and immune cells during infection
and can regulate the immune cell response.
"They can affect the half-life of T cells and the antigen
presenting cells and change the way that the killer T cells
get primed," Sarvetnick explains.
Some of the basic questions are which T cells are involved,
how the pancreas tries to defend itself in response to the
infection, which antigens are presented by B cells, and what
the exact nature of the T cell response is.
Sarvetnick's laboratory has already demonstrated that certain
cytokines produced at certain times of infection can lead
to the development or inhibition of diabetes in their models.
For instance, the molecule Interleukin–4 has a potent
inhibitory effect on the development of diabetes in pancreases
with cells expressing the molecule.
The current thinking is that the interleukins interfere
with the development of specific killer T cells, but the exact
mechanism of this inhibition is still unknown. As are the
mechanisms of other regulatory effects perpetrated by the
other regulatory molecules involved.
"There are really a number of things [the cytokines] do
that we are looking at," says Sarvetnick.
Other Therapeutic Implications
Another possibility for treating the disease is to understand
and manipulate the growth of the pancreas. One of the great
success stories in treating Type 1 diabetes in the last 35
years has been the pancreas transplant, in which a healthy
organ from a donor replaces the pancreas of a diabetes patient.
However this is a major, complicated surgery, limited both
by its inherent risk and the low availability of donor organs.
Perhaps a better approach would be some sort of therapy that
would regenerate the insulin producing islet cells in the
pancreas of a person with Type 1 diabetes—to use pluripotent
stem cells to replace the needed b
cells within a patient's own pancreas. This may even eventually
be a cure for the disease, though years away at best.
For now, the first step is the identification and isolation
of pancreatic progenitor cells. These are the progenitor cells
that differentiate to become insulin producing islet cells
in the pancreas. They can be identified and isolated through
flow cytometry through their unique cell-surface molecules—markers
which are yet to be identified.
A closely related issue is the elucidation of the molecular
signals that are involved in the differentiation of stem cells
into the islet b cells. The
ErbB receptors, for instance, seem to be implicated in this
process. At the moment Sarvetnick's laboratory is busy characterizing
the role of these receptors in the development and regeneration
of the pancreas.
Mother of Invention
As our interview is wrapping up, the phone rings. As if
by the tone of the buzz, Sarvetnick breaks off in mid-sentence
and wheels around to her office door. "Is that ...?" she asks.
Yes. Sorry—must take this call. Hello.... OK.... What
time?.... Talk to you later then....
"That's the other side of my life," she says when she puts
down the phone.
Then she tells me a story. This time it is not a story about
cells and viruses but about a working scientist, her daughter,
and her two sons—a tale of theatre, ballet classes, and
hockey practices. The story seems even more complicated than
the science she has been telling me about, involving a daily
ritual of coordinating schedules, arranging for school pick-ups
and drop-offs, helping with evening homework, and making sure
meals are covered. She tells me about the sacrifices she has
to make so that neither her children nor her research suffer.
Her science and her children are her life.
"You really pare your life down to the bare necessities,"
she says. "And it's not easy. It's really hard and trying."
"Ok it's murder." She says. But I know that by murder she
means happiness.
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