B
orn and raised in Kenya, Avnika
Ruparelia moved to Australia with
the hope of becoming a doctor.
When her application to medical school
was denied, she switched her focus to bio-
medical science. As someone who hates
the sight of blood, the career diversion
suited her. Ruparelia, now a research fel-
low at Monash University in Melbourne,
revels in “the feeling of being the only per-
son who knows that one thing,” she says.
“It’s absolutely fantastic.”Ruparelia got her start in research as an
undergraduate in the lab of Monash muscle
biologist Robert Bryson-Richardson. In 2009,
she worked with him to map a gene that even-
tually was linked to myofi brillar myopathies
(MFM), a group of diseases resulting in pro-
gressive muscle weakness that is character-
ized by protein clumping and structural failure
within muscle cells. As Bryson-Richardson and
Ruparelia began studying MFM, they and col-
leagues developed a zebrafi sh mutant model
for one type of the disease, fi lamin-related
MFM.^1 This model allowed researchers to
study not only fi lamin-related MFM, but also
the normal function of fi lamin C, a protein
found within skeletal muscles.
A year after developing the model,
Ruparelia focused on a diff erent form of MFM
called BAG3-related MFM. Unlike other forms
of the condition, this one is caused by muta-
tions in a gene that plays no obvious role in
muscles. The protein encoded by BAG3 nor-
mally helps dispose of malformed proteins. By
expressing mutant and normal forms of BAG3
in zebrafi sh, Ruparelia and her colleagues
found that the mutant form of the protein
trapped and sequestered the functional
form, eventually leading to muscle
damage.^2 Ruparelia, who fi nished
her PhD at Monash in 2014,
also found healthy BAG3
ensnared within aggre-
gates of mutant fi lamin
protein. BAG3, how-
eve r, wasn’t working
to clear the prob-
lematic proteins from
the muscle cells. In fact,
its presence within such clumps
seemed to inhibit other cell-cleansing
pathways as well.^3
“It’s important to question the results
you get and look for other explanations,
not just the one you set out to test,” says
Bryson-Richardson. Ruparelia, he adds,
is thorough in questioning her results.Their work allowed the pair to use a
zebrafi sh model of BAG3-related MFM to
run a drug screen to test potential therapies
for the disease. Some of the drugs the
researchers have identifi ed helped zebrafi sh
models with not only the pathology but also
the muscle weakness associated with the
disease. One of the drugs they’re testing is
already FDA-approved to treat other con-
ditions, which might mean it could move
through clinical trials much more quickly
than entirely new medicines.
“I’ve been impressed by Avnika because
she’s had a very focused line of research
in terms of the way that she’s approached
problems and built up a very strong body
of evidence to support that direction,”
says her mentor for the past two years
Gordon Lynch, a muscle biologist at the
University of Melbourne.
Ruparelia is now setting up the fi rst lab
in Australia to use African killifi sh as a model
organism. She spent the summer in geneticist
Christoph Englert’s lab at the Leibniz Institute
on Aging in Germany to learn how to use the
model and to gather some preliminary data.
The killifi sh’s short lifespan, Englert writes in
an email to The Scientist, will help Ruparelia
study the eff ect of aging on the regenerative
capacity of muscle.gREFERENCES- A.A. Ruparelia et al., “Characterization
and investigation of zebrafi sh models of
fi lamin-related myofi brillar myopathy,”
Hum Mol Genet, 21:4073–83, 2012.
(Cited 20 times) - A.A. Ruparelia et al., “Zebrafi sh models of
BAG3 myofi brillar myopathy suggest a toxic
gain of function leading to BAG3 insuffi -
ciency,” Acta Neuropathol, 128:821–33, 2014.
(Cited 27 times) - A.A. Ruparelia et al., “FLNC myofi brillar
myopathy results from impaired autoph-
agy and protein insuffi ciency,” Hum Mol
Genet, 25:2131–42, 2016. (Cited 15 times)
SCIENTIST TO WATC HAvnika Ruparelia: Muscle Mender
© CORWIN VON
KUHWEDE
09.2018 | THE SCIENTIST 59Research Fellow, Australian Regenerative Medicine Institute, Monash University, Age: 30IBY SUKANYA CHARUCHANDRA