56 THE SCIENTIST | the-scientist.com
PROFILECHRIS THEKKEDAMF
or Angela Dulhunty, the main draw of studying cells’ electri-
cal properties was the reward of instantaneous data. Rather
than having to wait sometimes days to get the results of a
biochemistry experiment, with electrophysiology “you see what
is happening in an individual cell in the moment,” says the mus-
cle biology researcher and now emeritus professor at Australian
National University in Canberra.
Dulhunty was attracted to learning how muscle works as an
undergraduate student studying physiology and biochemistry at
the University of Sydney. “Biochemistry in those days was a lot
of learning metabolic cycles, which was not as intuitive for me as
understanding how the micro-components of tissues and organs
inform their functions,” she says.
Dulhunty’s first real lab experience was during her final year
as an undergraduate. She was completing her honors thesis,
studying how hearing is registered by the ear and translated into
electrical signals through the nervous system.
She liked the hands-on lab work as much as the intellectual
exercise of cogitating on a biological problem. “I don’t think you can
separate the lab work from the thinking part of research. I’ve always
enjoyed putting the two together,” she says. This was among the
reasons Dulhunty continued to do her own hands-on experiments
in the lab, long after she started her own laboratory back in 1975.
In 2000, she made what she calls a “completely unexpected
and serendipitous discovery.” Dulhunty and her colleagues were
studying how the ryanodine receptor, a type of protein receptor,
functions in muscle cells. Ryanodine is an ion channel, embedded
in an internal membrane within the muscle cell, that surrounds a
pocket of calcium ions. The channel regulates the changes in cal-
cium ion concentration that control the muscle contractile appa-
ratus and, in turn, muscle movement.Dulhunty had set up electrophysiology experiments on a
receptor from mammalian cardiac muscle fiber to measure its
activity, and her initial measurements on the receptor’s activity
were going nicely. On a whim, she decided to add the enzyme
glutathione transferase to the muscle cells’ medium, just because
the chemical was sitting on the lab bench next to her. “I had an
extra 20 minutes to play, and I thought, ‘What would happen if Iadded the enzyme? Would it interact with the ryanodine recep-
tor?’” Dulhunty recalls.
She did not expect anything to happen, but the addition of
the enzyme blocked the cardiac ryanodine receptor’s function.
“I could see immediately that the glutathione transferase began
to inhibit the cardiac muscle receptor’s activity,” she recalls.
Because the effect was unexpected, she didn’t believe it initially
and repeated the experiment several more times to make sure
the results were real. Within a few months, Dulhunty and her
colleagues published their first paper on the role of the omega
class glutathione S-transferase, GSTO1-1, in inhibiting the ryano-
dine receptor in cardiac muscle and in increasing the activity of
the skeletal muscle ryanodine receptor. The team continued the
work: finding the part of the GSTO1-1 molecule responsible for
inhibiting the ryanodine receptor, they modified the molecule for
maximum efficacy. They also explored its potential as a therapeu-
tic drug for use in preventing cardiac arrhythmias. Three years
after the initial discovery, they found that another protein struc-
turally related to glutathione transferases, a chloride intracellular
ion channel, CLIC-2, could also dampen the activity of the ryano-
dine receptor in the heart. This was the start of Dulhunty’s work
to discover the significance of these proteins in muscle.
Throughout her career, Dulhunty has been driven by her curi-
osity to know how the underlying physiology of the body works,
and, as a result, has made important discoveries about how skel-
etal and heart muscle contractions are generated and regulated.AN EARLY STAR T
Dulhunty was born in 1946 in Sydney, Australia, an only child.
Her father was a geologist at the University of Sydney, and her
mother had been a sheep farmer and breeder prior to getting
married. Dulhunty was a “tomboy,” who couldn’t wait to get home
from school, change into shorts, and run around and climb trees
in the Australian bush with her friends, she says. Thanks to her
father, Dulhunty was also interested in science from an early age,
which led her to study biochemistry when she entered the Univer-
sity of Sydney in 1965. She also began riding horses as a young-
ster, and every summer during university she was a counselor and
instructor at a horse riding camp in the Snowy Mountains, close
to where she now lives just outside of Canberra.
When wrapping up her undergraduate studies, Dulhunty
thought she wanted to go to medical school so that she could do
medical research, but a professor of biochemistry advised her to
attend graduate school instead if research was her main interest.Having pioneered the study of muscle physiology in mammals,
Angela Dulhunty uncovered how ion channels enable muscle movement.BY ANNA AZVOLINSKYAll Muscle
I don’t think you can separate the lab work
from the thinking part of research. I’ve always
enjoyed putting the two together.