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Mathematical Biology seminar
Kathleen Clark
Research Assistant Professor
Dept. of Biology and Huntman Cancer Institute
University of Utah
"Flies have muscle? Using flies to study human muscle disease"
April 21, 2004
3:05pm in LCB 215
Abstract: Muscle cells respond to increased demand for work output by
growth
and remodeling. This indicates that muscles have a biomechanical sensor
that
can detect changes in muscle stretch, and direct changes in gene
expression
and cellular organization. Mutations in proteins important for sensor
function would impair the growth/remodeling process, leading to muscle
failure. Stretch and other forms of mechanical stress are likely sensed
at
anchor points present in the contractile apparatus; when muscle
contracts or
is stretched, these anchor points are the main conduits of the
mechanical
forces produced. Thus, proteins present at these sites may be components
of
the biomechanical sensor. We are studying proteins that have features
suggestive of a function in the biomechanical sensor. One of these
proteins
- Muscle LIM protein (MLP), is present at the anchor sites, but can also
be
found in the nucleus, suggesting that it might shuttle between these two
cellular compartments, to convey information from the sensor to the
nucleus.
In fact, mutations in MLP lead to dilated cardiomyopathy and
hypertrophic
cardiomyopathy - two forms of heart failure that result from aberrant
remodeling of the heart. We are using the genetics system of the fruit
fly,
Drosophila melanogaster, to test specific hypotheses about MLP function.
For
example, we are testing whether MLP needs to be able to reside in the
nucleus in order to function. In addition, we can take advantage of the
genetic tools available in the fly to find other proteins that function
with
MLP. This information will help us to determine the molecular pathway in
which MLP acts. Using these types of experiments, we hope to confirm
that
MLP is part of the biomechanical sensor, and moves into the nucleus in
response to increased muscle load. In addition, we should be able to
identify other components of the sensor, which may represent
uncharacterized
mutations responsible for cardiomyopathies.
For more information contact J. Keener, 1-6089
E-mail:
keener@math.utah.edu
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