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Research Recognitions & Achievements
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Fully Biodegradable PFO/ASD Occluder
PHOTO: MSE
Atrial septal defect (ASD) and patent foramen ovale (PFO) are forms of heart defects which result in blood flow between
the left and right atria via a “hole”. MSE Professors Subbu Venkatraman and Freddy Boey’s concept of a biodegradable
occluder does not only close the hole, but also provides a temporary scaffold for the in-growing host tissue to cover
the device and the defect underneath. The device may degrade into nontoxic ingredients and be fully absorbed, leaving
“native” tissue behind. This concept can minimize the potential for future complications caused by the presence of a foreign
body and subsequently provide the possibility of unobstructed trans-septal access. These results showed clearly that it is
feasible to replace the current non-degradable devices with the new generation biodegradable ASD/PFO occluder.
^ (a) The Chinese Lantern PFO/ASD prototype and model;
(b) The histology image indicates high biocompatibility of the device in pig at one month.
Quantitative Time-course Profiling of Parasite and Host Cell Proteins in
the Human Malaria Parasite Plasmodium Falciparum
the scientists were able to unravel
many intricate biological processes
that could be used as targets for
development of new anti-malarial
drugs. Given the fact that malaria until
today, affects close to 1/3 of the world
population and kills over 1 million
people every year, these results will be
a major contribution to the worldwide
effort of improving human health.
PHOTO: MSE
In the early 2010, the research group
of Dr Z. Bozdech has published a
paper in the prestigious journal of
Nature Biotechnology in which they
described malaria parasites behaviour
in many different stress conditions
including the treatments with basic
malaria drugs. Activity of every single
gene in the genome was monitored
using the sophisticated technology
of Deoxyribonucleic acid (DNA)
microarrays for malaria parasites,
a platform established at NTU five
years ago. Based on these results the
researchers were able to reconstruct
an interacting network of all proteins
and thus describe the physiology of
plasmodium parasites (see figure).
Using methods of systems biology
(also known as integrative biology),
^ The global picture of malaria parasite gene activity in different stress conditions
and drug exposures (red ~activated gene, green ~ deactivated gene).
NTU Research Report 2010/11 65
Research Recognitions & Achievements
PHOTO: SBS
A New Level of Quality in Representing Biological Molecules of Atomic
Resolution
^ Platform to design new experiments and therapeutic agents
Associate Professor Wolfgang Müller-Wittig, Fraunhofer IDM@NTU and Professor Gerhard Grüber, School of Biological
Sciences (SBS), NTU, developed a communication platform for the planning, interpretation and presentation of three-dimensional
visualization of proteins, involved in energy production and diseases.
Specialists can read in their experimental data and analyze and evaluate these complex 3D protein structures interactively. The
use of a multi-touch table allows an intuitive interaction with the dynamic proteins on an atomic level. In addition, the visualization,
probing, and manipulation of such complex processes provide a new learning environment. Finally, the virtual representation
presents a communication platform, enabling engineers and manager to discuss future projects. This new technology has been
presented at the world’s largest computer exhibition, CeBIT in Hanover, Germany, in March 2010 and 2011.
Angiopoietin-like 4 is Essential for Tumour Survival
NTU researchers have discovered
that the growth of cancer cells can be
avoided and tumours can be reduced by
controlling the ratio of superoxide and
hydrogen peroxide within tumour cells.
A study led by Assistant Professor
Andrew Tan from School of Biological
Sciences (SBS) identifies tumourderived angiopoietin-like protein 4
(ANGPTL4) as a novel player in redox
cancer biology. They showed that
elevated ANGPTL4 expression is a
common feature in human tumours.
Representative picture of tumours >
induced by control (left) and ANGPTL4deficient cancer cells (right) in nude
mice at 8 weeks post-inoculation.
They have demonstrated a novel role of
tumour-derived ANGPTL4 that confer
anoikis resistance and sustain tumour
growth via an autocrine adhesion
mimicry. Their findings that the inhibition
of ANGPTL4-mediated redox signalling
induces tumour cells death highlights
ANGPTL4 as a novel tumour biomarker
and emphasizes that anticancer
therapeutics focused on redox-based
apoptosis induction in tumour is an
exciting and viable strategy.
^
Zhu, P.C., Tan, M.J., Huang, R-L, Tan, C.K., Chong, H.C., Pal, M., Lam, C.R.I., Boukamp, P., Pan, J.Y., Tan, S.H., Kersten, S., Li, H.Y., Ding, J.L. and
Tan, N.S. (2011). Angiopoietin-like 4 proteins elevates the pro-survival intracellular O2-:H2O2 ratio and confers anoikis resistance to tumor. Cancer Cell
19:401-415. (IF: 25.288)
This article was previewed in Cancer Cell. Terada, L.S. and Nwariaku, F.E. (2011) Escaping Anoikis through ROS: ANGPTL4 controls integrin signaling
through Nox1. Cancer Cell 19(3): 297-299.
This work was also selected to be highlighted n Nature Chemical Biology “Reactive oxygen signals: contact-independent growth, 2011, vol7(5) pg 247”
This work has been featured in Channel 8 (News Tonight, 16 Mar 2011, 10pm) and Channel U (News Tonight, 16 Mar 2011, 11pm) and also in several
high profile websites including SciBX under the category Distillery: Therapeutics : March 31 2011, Volume 4 / Number 13 (http://www.nature.com/
scibx/journal/v4/n13/full/scibx.2011.362.html.)
66 NTU Research Report 2010/11
Research Recognitions & Achievements
Advance toward Controlling Fungus that Caused Irish Potato Famine
The Phytophthora fungi are known to cause extensive damage to food crops such
as potatoes and soybeans, as well as to ornamental plants like rhododendrons.
PHOTO: SPMS
A team led by Professor Loh Teck Peng, School of Physical & Mathematical
Sciences suggests that a synthetic version of the most biologically active form
known as (3R,7R,11R,15R)-α-1 could provide the basis for developing a way to
control the fungus. The research also showed that they could make relatively large
quantities of the hormone, which could open the door to an effective method to
fight this ancient scourge.
^ Potatoes and other crops may get protection against a devastating plant disease that caused the Irish potato famine. Credit: iStock
NTU scientists engineer suicide bacteria to kill superbug
Assistant Professors Matthew Chang
and Poh Chueh Loo, both from School
of Chemical & Biomedical Engineering,
have for the first time re-engineered
a harmless strain Escherichia coli
(also known as E. coli), a common
bacterium found in the human digestive
system, to seek out and kill other
dangerous bacteria. The engineered
“suicide bacteria” fights against the
superbug Pseudomonas aeruginosa
– a highly resistant bacteria strain that
causes infections in the eyes, ears,
gastrointestinal tract and urinary tract.
The biochemically engineered E. coli,
upon detection of the other bacterium,
will generate “killing molecules” within
them, and will self-destruct, releasing
the molecules to kill the aeruginosa.
These “killing molecules” are deadly for
the superbug, but harmless to the human
body. The breakthrough discovery
is a step forward in advancing the
treatment and prevention of infections,
as unlike today’s broad-spectrum
antibiotics which kill both good and
bad bacteria, this revolutionary method
is a precise approach targeting only
harmful bacteria.
^Schematic of ‘Pathogen Sensing and Killing’ system. The sensing mechanism is activated by intercepting signaling molecules naturally produced by Pseudomonas aeruginosa, a human pathogen. This activation leads to the production of the killing protein effective against P. aeruginosa, and the production of the lysis protein that bursts the E. coli cells open. After the lysis protein attains the threshold concentration that causes the cells to burst, the accumulated killing molecules are released into the environment and kills P. aeruginosa.
Novel research set to pinpoint risk of heart attacks and strokes
Coronary heart disease and stroke are
major worldwide health problems. In
Singapore, it accounts for more than
30 per cent of all deaths, with about
15 people dying daily because of heart
attack and stroke. NTU researchers
led by Assistant Professor Newman
Sze in partnership with Interuniversity
Cardiology Institute of the Netherlands
(ICIN)’s lead cardiology scientist
Professor Dominique de Kleijn and
lead clinicians Professor Lee Chuen
Neng and Dr. Vitaly Sorokin of the
National University Hospital (NUH)
are working on a blood test kit that
can predict the chance of a person
having a heart attack in the future.
The team have earlier discovered
more than 10 types of unique proteins
which are commonly present in
the blood of a person who recently
suffered a stroke or heart attack. They
have since embarked on identifying
proteins called biomarkers that can
be used to pinpoint people at risk of
cardiovascular disease. The more
such biomarkers are found in the
blood, the higher the risk of a heart
attack or stroke. Using the Agilent
HPLC-Chip LC/MS Triple Quadrupole
system, the team will also be able to
validate over 100 biomarkers in one
year, as compared to 10 biomarkers
over five years using the conventional
method. Their research is expected to
result in the development of a sensitive
diagnostic tool – possibly in the form
of a simple blood test - which can
detect these bio-markers so as to help
pinpoint the risk of heart diseases in a
person before it happens.
^ Professor Sze working with Agilent
NTU Research Report 2010/11 67
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