Athens, Ga. – The National Institutes of Health have
awarded, as part of the American Reinvestment and Recovery Act, a two-year, $2
million grant to a University of Georgia genetics researcher and her colleagues
for studies on the thymus, the organ in humans that produces disease-fighting
T-cells.
Nancy Manley, a professor of genetics and chair of UGA’s interdepartmental
biology group, is the principal investigator on the grant, which will support
studies on molecular mechanisms regulating thymic epithelial cells during
aging. The new grant supports a collaborative program between UGA, the
University of Texas M. D. Anderson Cancer Research Center in Science
Park, Tex., and the Center for
Stem Cell Research at the University
of Edinburgh in Scotland.
Other principal investigators are Ellen Richie, professor of
carcinogenesis (Texas) and Clare Blackburn, group leader (Edinburgh).
“This research is an excellent example of how the stimulus
money is providing jobs in science and, at the same time, helping unravel new
findings that could be important for human health,” said Manley.
The grant will allow Manley to hire two research scientists,
a laboratory technician and a full-time administrator.
The subject of intense interest and extends and expands work
in which Manley has been involved for some years now.
Last year, Manley’s lab, using the mouse as a biological
model, provided the first evidence that a key gene may be crucial to
maintaining the production of the thymus and its disease-fighting T-cells after
an animal’s birth.
The discovery could help scientists find out how to turn the
thymus back on so it could produce T-cells long after it normally shuts down
most of its function, which, for humans, occurs by early adulthood. If the
finding leads to further ways to manipulate the gene, the result could be a new
avenue for the body to fight disease more effectively as it ages.
“Such things as infectious diseases, inflammation and heart
problems are all related to immune response,” Manley said last year. “You don’t
have to think far to see how understanding the effect of this gene could affect
the quality of life for older people and others as well.”
The newly funded research will try to discover the actual
mechanisms by which the thymus shuts down and how these changes affect immune
system function during aging. If and when that mechanism is found, scientists
may find a way to turn the organ’s function back on permanently or at specific
times in the life of a human or an animal to fight disease or aging. An
ultimate payoff might be longer and healthier lives for people.
The thymus is an organ located in the upper part of the
human chest cavity, behind the sternum. This organ is the location where
important systemic infection fighters called T-cells develop. Over the past two
decades, T-cell counts have become part of everyday dialogue due to their
importance in monitoring HIV/AIDS and other disorders.
The thymus slowly begins to shut down early in life and
becomes largely inactive by early adulthood. Still, that’s fine for most
people, since an entire lifetime supply of T-cells is produced in that time.
But, for some people, the loss of irreplaceable T-cells through disease can
lead to chronic illnesses and a shortened life.
Until recently, scientists had thought that the thymus after
birth was unable to regenerate T-cells because no known regulatory mechanism
existed that might allow doctors to “turn back on” the thymus if a person’s
T-cells were compromised. There are now, however, some treatments currently in
trials that can transiently rejuvenate the thymus and increase thymic output in
humans.
The problem has been, though, that the mechanisms by which
all this works are poorly understood, and all current treatments have systemic
effects that can cause unacceptable side effects in all but the most seriously
ill, who are more willing to tolerate them in exchange for possible benefit.
“So far, the possibility of this working looks very good,”
said Manley.
While the mouse model doesn’t precisely mimic human
response, it is close enough so that biologists and geneticists can often draw
conclusions from mouse trials on how humans will respond.
Though the ability of science to manipulate this gene and
potentially the production of T-cells isn’t going to happen next week, it may
not be that far down the road, either. Under best circumstances, the
researchers should know within five to 10 years whether the therapeutic ability
to turn back on the production of T-cells is possible.
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Note to editors:
This release uses material from an earlier release on Manley’s research.