We welcome Australian, New Zealand and International students
who would like to join in these studies, either as a part of laboratory
experience for undergraduate courses, for Honours projects or for Masters
or PhD studies. Interested students should contact angela.dulhunty@anu.edu.au
or go to http://jcsmr.anu.edu.au/students/index.php
for more general information.
The Muscle Research Group studies molecular interactions
between two Ca2+ ion channels that underlie Ca2+ signalling in muscle.
The channels are the dihydropyridine receptor (DHPR) Ca2+ channel in the
surface membrane and the ryanodine receptor (RyR) Ca2+ release channel
in the sarcoplasmic reticulum (SR) Ca2+ store. These proteins are essential
for movement. Excitation-contraction (EC) coupling is broadly defined
as the signal transduction process that links an action potential to contraction,
but more narrowly encapsulates the processes that intervene between depolarization
of the surface membrane and Ca2+ release from the SR. EC coupling in the
heart depends on RyR activation by Ca2+ ions that enter through the DHPR
ion channel. In marked contrast EC coupling in skeletal muscle does not
depend on external Ca2+. Instead, a depolarisation-dependent signal is
transmitted from the DHPR to the RyR by conformational coupling between
the two proteins. Proper Ca2+ signalling depends (a) the activity of the
RyR during EC coupling and (b) on the amount of Ca2+ available for release
within the Ca2+ store. The factors that set RyR channel activity and the
Ca2+ load within the store are the focus of our investigations.
Although many of our questions are very basic, the research is increasingly
directed to understanding disease-related mutations in the proteins that
are linked to debilitating skeletal myopathies and to fatal cardiomyopathies.
The long term goal in this regard is the rational design of drugs that
might help alleviate the symptoms of these disorders.
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