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@ U S T . H K
way regulate their response to different
light conditions; and helped research
into disorders such as night blindness
and retinitis pigmentosa. (
Cell
, 2011)
Digestive Aid
The Zhang Lab has assisted in the
identification of gene mutations that
may cause digestive diseases. The team
recognized the striking similarities, both
in appearance and mechanistic features,
between two structures in separate
parts of the human body that perform
vastly different functions. Stereocilia
are organelles of hair cells that respond
to fluid motion for different functions in
the human body, including hearing and
balance. Brush border microvilli, located
on the surface of epithelial cells in areas
such as the small intestines and proximal
Myosin VIIa is a motor
protein responsible for
transporting various
cargos in living cells and
maintaining stereocilia
structures in hair cells.
Genetic mutations in the
cargo-binding tail of
myosin VIIa, in complex
with adaptor protein Sans,
can cause Usher syndrome,
a genetic disorder resulting
in hearing and vision loss
or impairment.
tubules of kidneys, are cellular membrane
protrusions that increase cells’ surface
area and help with absorption, secretion,
and cellular adhesion. Findings showed
that both systems use very similar sets
of proteins to organize their multi-
protein complex, building tip-links
that can sustain mechanical strains.
Current knowledge of stereocilia tip-link
complex is more advanced than that
of microvilli tip-link complex, thus by
identifying the similarity between these
two systems, existing understanding
of the former may provide insight
into understanding of the latter. They
anticipate that this characterization will
assist understanding of certain gut or
kidney diseases. (
Developmental Cell
,
2016; and
PNAS
, 2017)
Research into the mechanisms underlying the
light-detecting capabilities of fruit flies (drosophila)
led to insights on human visual disorders.
Deciphering Proteins
The mysteries of the vastly complex
world of proteins are being unraveled
through many different structural biology
advances at the Zhang Lab. The following
highlights several key discoveries:
Hereditary Deafness
and Blindness
Researchers have systematically elucidated
proteins (for example, myosin I, myosin
III, myosin VI, myosin VII, myosin X, and
myosin XV) and protein interaction
networks (for example, the Usher complex)
that are required for the proper
development and function of sound-
detecting hair cells in human ears and
light-receiving photoreceptors in human
eyes. This work led to significant
findings that mutation of myosin VIIa
can affect the proper development
and normal functioning of hair cells in
human ears and eyes which can lead
to severe deaf-and-blindness (Usher
syndrome) in new-borns and young
children. (
Cell
, 2009;
Science
, 2011;
Nature Structural and Molecular Biology
,
2015;
eLife
, 2016; among others)
Using fruit fly photoreceptors as
a model, Prof Zhang and his team
found that the INAD scaffold protein
in microvilli of photoreceptors in
animal eyes can undergo a light-
dependent architectural or molecular
shape change, regulating light signal
detection speed and signal output
amplitude, as a result of a rapid
oxidation/reduction cycle. The finding
expanded understanding of how animal
photoreceptors can detect such a broad
intensity of light signals at a very rapid
speed and how human eyes in the same
Myosin VIIa mutant
Wild type
Protein interaction networks in brush border microvilli (Figure A) and inner ear stereocilia (Figure B).
Prof Zhang’s studies characterized interactions biochemically and structurally in microvilli
and discovered that microvilli and stereocilia tip-link complexes are strikingly similar.
A. Intestine brush border microvilli
B. Inner ear hair cell stereocilia
