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Research Recognitions & Achievements Future Healthcare 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 Nanyang Technological University Research Support Office 76 Nanyang Drive, N2. 1-B4-01, Singapore 637331 Phone: (65) 6790 5637 Fax: (65) 6791 2397 Website: http://research.ntu.edu.sg Reg. No. 200604393R