R E S E A R C H @ H K U S T
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differentiation (
PNAS
, 2012). The work
has potential for novel therapeutic
agents related to leukemia.
As an international front-runner
in NMR methodologies, Prof Zhu has
steered the University’s Biological NMR
Center since arriving at HKUST in the
mid-1990s, advancing and leveraging
the institution’s world-class 500, 750
and 800 MHz NMR spectrometers to
study, design, and develop experiments
to reveal novel aspects of the molecular
cosmos.
His leading work on NMR
methodologies, for example the
transverse relaxation-optimized spec-
troscopy (TROSY)-based methods,
for the study of large biomolecules in
solution was published in an array of
papers from 1998 to 2002 in journals
such as
Angewandte Chemie International
Edition in English, Journal of Biomolecular
NMR,
and
Journal of Magnetic Resonance
as well as included in textbooks. The
biomolecular community now routinely
uses some of these techniques. The work
also gave HKUST an early global edge in
NMR-based structural biology discovery.
Work is ongoing in developing the
next-generation of NMR technology.
One avenue is to shorten NMR
experimental time for studying fast
biomolecular systems with new super-
resolution algorithms. Prof Zhu is
excited about its potential but not ready
to reveal just yet how it may reshape the
structural biology landscape!
NMR structure of Cdt1/Mcm6 complex solved by
Prof Zhu provides insight into how mutations can
disrupt the Cdt1-Mcm6 interaction and lead to
impaired DNA replication. This provides a possible
target for designing anti-cancer drugs.
the structure of the Cdt1/Mcm6 complex
through NMR spectroscopy. The team
was the first to reveal the details at
atomic resolution of how the complex
binds and how mutations can disrupt this
interaction, impairing DNA replication
(
Journal of Biological Chemistry
, 2010;
Nucleic Acids Research
, 2012), and
providing a possible target for designing
anti-cancer drugs. His collaborators on
such work included Prof Chun Liang,
Division of Life Science, who is interested
in regulation of DNA replication both in
normal cells and in relation to cancer;
and Prof Bik Tye, who uses cryo-EM
structures to map out the important
interaction regions for Prof Zhu to
delineate detailed structure-functions
through NMR spectroscopy.
Prof Zhu’s researchers also discovered
the role of histone methyltransferase
SET8 (
Cell Cycle
, 2008) and thus a new
regulator suppressing DNA replication in
the human cell cycle. The team is currently
studying the Epstein-Barr virus (EBV),
which recruits human DNA replication
machinery for its own DNA replication
and can play a part in nasopharyngeal
carcinoma, a cancer of special relevance
to southern China. In studying the
interaction of EBV protein EBNA1 and
human proteins, Prof Zhu is seeking to
understand the binding mechanism used
by the virus to explore the possibility of
designing drugs to block virus replication
in human cells and thus the disease.
In addition, his group’s studies of
the structure-functions of the Hox/
Geminin complex have helped reveal
how the geminin protein plays a role
in balancing cell proliferation and cell
The Hayflick limit showed
a normal human cell can
divide around 60 times. But
by searching and understanding
the molecular mechanisms setting this limit,
could there be a way to extend this limit and
hence, prolong a human life?
PROF GUANG ZHU
Professor of Life Science
