09.2018 | THE SCIENTIST 57ANGELA DULHUNTY
Emeritus Professor, John Curtin School of Medical Research,
Australian National University, Canberra, Australia
Honorary Member, Australian Physiological Society
President of the Australian Society for Biophysics (ASB, 2010 – 2012)
Founding director of Biotron Pty Ltd, a biotechnology company
Head of the John Curtin School of Medical Research Department of
Molecular Bioscience (previously Division of Biochemistry and
Molecular Biology, 2007-2014)
Greatest Hits
- Along with Clara Franzini-Armstrong, uncovered that
caveolae—tiny pocket structures in the surface membrane
of individual muscle fibers whose function was previously
a mystery—allowed muscle to stretch to more than double
its length without incurring damage - By developing techniques of muscle electrophysiology,
pioneered the study of mammalian muscle biology - Found that potassium and chloride ion activity in muscle
contraction differs drastically between amphibian and
mammalian muscle - Established that specific members of the glutathione
transferase structural family differentially modulate the
activity of calcium-dependent ryanodine receptors in
cardiac and skeletal muscle - Found that a mutation in the type 2 chloride intracellular
ion channel (CLIC-2) in humans can result in an X-linked
human disorder
After seeking advice from other professors, she ended up in Peter
Gage’s membrane physiology and neuroscience lab at the Univer-
sity of New South Wales in Sydney. “He was exciting to talk to and
an inspiring scientist,” Dulhunty says.BASIC QUESTIONS
Dulhunty began her PhD in 1969, getting straight to work on
her thesis, as no coursework was required for a graduate degree
in Australia at the time. She initially worked on characterizing
a deadly toxin secreted by the Southern blue-ringed octopus
(Hapalochlaena maculosa), which lives in tidal rock pools along
the southern coast in Australia. Using live octopuses, Dulhunty
found that the water-soluble maculotoxin inhibits action poten-
tials in motor nerves and muscle fibers, preventing the transmis-
sion of neuromuscular signals.
Dulhunty also began her initial work on the biophysical prop-
erties of muscle fibers, which contract in milliseconds based on
the translation of signals from the brain to the muscle. “The basic
question,” she says, “was, how does the electrical signal on the sur-
face of the muscle fiber get translated into a muscle contraction?
And that is still what I am working on today!”
In the 1970s and 1980s, Dulhunty—and most labs studying
muscle—used individual toad or frog muscle fibers for electrophysi-
ology experiments because the animals have robust muscle fibers
that can be dissected and separated relatively easily. “Mammalian
fibers are much harder to work with. It is very difficult to separate
out an individual fiber because they are much longer, and there is
so much surrounding connective tissue,” Dulhunty explains.BEYOND THE LIMIT
After completing her PhD in 1973, Dulhunty applied for and was
awarded a postdoctoral fellowship from the Muscular Dystrophy
Association of America and had her first overseas adventure. Dul-
hunty worked at the University of Rochester in New York in the
lab of Clara Franzini-Armstrong, who is now an emeritus pro-
fessor at the University of Pennsylvania. At the time, Armstrong
had already made her name in science by demonstrating how the
structure of the muscle fiber membrane facilitates its function.
Continuing to work on frog skeletal muscles, Dulhunty com-
bined her expertise in electrophysiology with Armstrong’s skills
in electron microscopy. “This in itself was remarkable at the time,
as the two vastly different techniques were generally not com-
bined into a single study,” she says. In 1975, Armstrong and Dul-
hunty uncovered a key function of caveolae, Latin for “little caves,”