NRF POC Awardees - 3rd Grant Call
(Feb 2010)
1. Improvement in Yield of Haemotopoietic Stem Cells (HSCs) via Automation and Optimization of the Umbilical Cord Blood (UCB) Collection Process with Further Stem Cells' Characterization
One of the current limitations for UCB collections lies with the high numbers (up to 30%) of collections with inadequate harvest of UCB volume and hence HSC numbers, and hence not useful for even use in paediatric patients. Moreover, the success of HSC transplantations is directly proportional to the cell dose transplanted. The main goal is to develop an effective UCB collection system to improve the yield (in terms of quality and quantity) of HSCs from the placenta. To enable this system for ready deployment in the hospitals and cord blood banks, the system components and its disposable accessories have to be carefully designed and tested.
Cord blood banks in Singapore have indicated to us that a novel device that complements their collection procedure for incremental harvest of HSC will be greatly desired. In this regard, the deployment of this proposed system, which supports multiple perfusions and minimum human handling, can improve the yield of stem cells from placentas for public cord blood banks (even with those cases with private cord banking). This would create more opportunities for finding the right match for transplantation purposes. The current reported collection methods do not support these novel functions.
In this study, our hypothesis is that more primitive HSCs may be liberated from the placenta using our proposed device, as compared to the current reported collection methods. There should be an increased expression of stem cell markers in the blood collected from the placenta, as the placenta is purportedly a stem cell niche. In this study, there is a need to characterize the primitive stem cells. This phase is critical for storage and transplantation purposes. To the best of our knowledge, such information on the primitive stem cells is not available yet. Further cell characterization and culture related work can thus be initiated from this project.
Dr. Tang received his B.Eng. (in 1998), M.Eng. (in 2000) and Ph.D. (in 2006) from the National University of Singapore. He is currently a research staff here. His research interests include new control, diagnostic and instrumentation methods for intelligent mechatronics, precision motion systems and biomedical systems, and new methodologies for adaptive neural control for the above mentioned systems.
2. CDH17 Marker as a Novel Target for Liver and Stomach Cancer Therapies
Liver and stomach cancers are among the most common and lethal malignancies in Singapore, China and Asia. These cancers are often asymptomatic in the early stages and so many patients are diagnosed at the very advanced stages at presentation, for which there are no effective therapies. To address such unmet medical needs, our team has employed cutting-edge genomic and proteomic methods to search for new biomarkers and drugs to target these tumors. CDH17 is a prominent cancer biomarker overexpressed in both cancer types but not in normal adult liver and stomach tissues. RNA interference targeting CDH17 marker is able to inhibit tumor growth and prevent metastasis. Since gene therapies are still experimental, our team is developing antibodies/phage peptides against CDH17 that can be used in biomarker assays to detect cancer earlier, and clinically as therapeutic agent to treat cancer patients. This is a collaborative effort involving dedicated clinicians, scientist and pharmacologist between NUS and NUH, and a potential joint venture with pharmaceutical companies. The ability to detect cancer at its early stage and to deliver targeted drugs to kill cancer cells can save many lives and enhance the quality of life of cancer patients.
John Luk received B.Sc.(Hon) at Hong Kong University and doctoral degree in Clinical Microbiology at Karolinska in Stockholm. His postdoctoral fellowship was done at Harvard Medical School in Tim Springer’s lab on cell adhesion molecules. He was assistant professor at Case Western Reserve University and associate professor at Hong Kong University before joining the National University of Singapore, where he leads a cancer pharmacology program with special focus on targeting the oncogenic signalling pathways in liver and stomach cancers. He received fellowships from EMBO, NATO, and Merck, filed 4 US patents on his discoveries and inventions, and published 130 papers including Cell, Nature Genetics, Gastroenterology, and Hepatology. Dr. Luk has mentored 16 PhD students and 8 postdoctoral fellows, and also appointed as honorary professor or advisor at top universities like Harvard, Peking, and Fudan.
3. Fluorescent-tagged Antimalarials as Commercial Molecular Probes to Diagnose Drug Resistance and to Study Diseases
A child dies from malaria every 30 seconds in Africa. Globally, this infectious disease claims 1-2 million lives every year, and drives a vicious cycle of disease and poverty in many national economies. It has resurged in the last 2 decades, primarily due to drug resistance. Even artemisinin, our last line of defence against the prime killer, Plasmodium falciparum, is starting to fail in the control of the malaria parasite. The debilitating and wide-spread malaria species, Plasmodium vivax, which predominates here in Asia, is rapidly developing resistance to chloroquine. Swift, reliable and accurate screening probes that facilitate the characterisation of drug resistance are urgently needed. Current methods to detect and study resistance are laborious, protracted, imprecise and bio-hazardous. We have synthesized a fluorescent-labelled chloroquine molecule with the unique ability to rapidly differentiate drug-sensitive from drug-resistant malaria strains with high specificity and sensitivity. We are also witnessing a global resurgence in the use of chloroquine to treat cancers, autoimmune diseases, viral (HIV, SARS, flu) and bacterial infections. We thus envisage an enormous demand by research and clinical laboratories for tools that allow visualization of chloroquine within cells. Multiple needs and opportunities in the domains of drug resistance detection and chemotherapy are clear. To meet such growing needs in the pharmaceutical, biotechnological, scientific and clinical sectors, we are developing fluorescent-labelled probes of the antimalarial drug, chloroquine, that will serve as invaluable diagnostic and research tools applied to a wide variety of diseases.
Dr. Kevin Tan pursued his PhD at the Department of Microbiology NUS and his postdoctoral studies at the Laboratory of Molecular Parasitology, The Rockefeller University, under the supervision of Professor George Cross. Upon his return to Singapore in 2003, he began his research on protozoan cell death focusing on PCD pathways in the enteric parasite Blastocystis and the malaria parasite Plasmodium falciparum. He also administers the national proficiency testing for malaria diagnosis in his capacity as the Director of the National Malaria Reference Centre. He is a member of the Singapore MIT-Alliance for Research and Technology’s Interdisciplinary Research Group on Infectious Diseases (SMART IRG ID), and his project is aimed at investigating the biomechanical aspects of malaria cell death. His other research interests include host-pathogen interactions, molecular mimicry and nanotechnological tools. More details on his research interests can be found at:
http://www.med.nus.edu.sg/mbio/staff-k_tan.html
Dr. Martin J. Lear received his PhD in Scotland under the guidance of David J. Robins at the University of Glasgow, UK. During 1995-2000, he won several postdoctoral fellowships (pharmaceutical, JSPS, CREST) and globe-trotted from the UK (Parke-Davis, Cambridge) to France (ISCN-CNRS natural products institute, Gif-sur-Yvette) and Japan (Tohoku University, Sendai). After four years as an Assistant Professor with Masahiro Hirama, he joined the Department of Chemistry and Medicinal Chemistry Program at the National University of Singapore in January 2005. His research interests focus on the chemical synthesis, molecular imaging and manipulation of natural products, glycolipids and drugs in our fight against malaria, tuberculosis, and cancer. For more details see
http://www.chemistry.nus.edu.sg/ourpeople/academic_staff/lear.htm
4. Development of a Novel Bioabsorbable Drug-Eluting Ventilation Tube for Chronic Middle Ear Infection
Otitis media, in which the middle ear traps fluid, is the single most common diagnosis for pediatricians. Annual costs approximate $5 billion for USA alone. In chronic otitis media (COM), problems include chronic hearing loss, language, academic and behavior problems, reduced quality of life, and impaired balance. Ventilation tube (VT) insertion for COM is the most common surgery performed in children by Ear Nose Throat specialists, with 2 million VTs placed in USA alone each year. Current VTs are made of plastic. Problems include clogged tubes, infected tubes, and residual perforation of the ear drum. The duration before the VT self-extrudes is also unpredictable, often resulting in the need for further surgeries for removal or insertion of new tubes under general anaesthesia, with their attendant anesthetic, surgical risks and costs. Post VT, patients need to avoid water getting into the ears whilst bathing or swimming.
This study aims to develop and patent a new ventilation tube for chronic middle ear infection with features to circumvent current problems: 1) Bioabsorbable -self absorbing predictably, with reduced clogging, tissue reaction, infection and ear drum perforation; 2) Drug-eluting to reduce infections; 3) One-way flow mechanism – to allow swimming and bathing without ear plugs; 4) Easily deployed in the clinic without general anesthesia.
Dr Lynne Lim is currently Associate Professor at NUS and Senior Consultant at NUH. She is the Director of the Centre of Hearing Intervention and Language Development at the Ear Nose Throat Department at NUH. She graduated from NUS Medical School in 1992, completed ENT specialisation in 2001, and sub-specialised in Cincinnati, America between 2001-2003 for Pediatric ENT and an NMRC Fellowship for Hearing Research. She completed her Master of Public Health Degree at the Harvard School of Public Health in 2005. Her current research focuses are in hearing loss and restoration, airway and novel biomedical products. This is the 2nd POC project she is working on with her co-PI, Prof Subbu Venkatraman, from NTU, with the 1st being a novel trachea stent.
5. Development of Efficient Methods for the Production of Biodiesel from Grease
Biodiesel refers to a non-petroleum-based diesel fuel consisting of short chain alkyl esters and is currently made by transesterification of vegetable oil. Great attention has been focused on the production of biodiesel from cheaper waste feedstock to reduce the cost, utilize the waste, and increase bioenergy capacity. This project aims to develop efficient methods for the production of biodiesel from grease, a low-cost waste collected worldwide in a large amount (e.g. brown grease is collected in Singapore at 800-1000 tons per year). Thus far, the efficient conversion of grease to biodiesel has been a technical challenge due to the high free fatty acid content in grease. This project will tackle the challenge by developing novel and efficient catalysts and catalytic systems such as magnetic nanoparticles-based acid catalysts and dual enzyme systems. The technologies and catalysts developed from the project could be utilized by our industrial collaborator Alpha Synovate for further development of industrial process.
Dr. Li Zhi has been an associate Professor at Department of Chemical & Biomolecular Engineering, National University of Singapore, since 2006. He received Ph.D. in Organic Chemistry from University of Vienna, Austria in 1991. After doing postdoctoral research at University of Oslo, Norway and ETH Zurich, Switzerland, he begun his independent research in biocatalysis in 1997 at the ETH Institute of Biotechnology and was promoted to a group leader in 1999. His current research focuses on biocatalysis and biotransformation for chemical and pharmaceutical syntheses, synthetic and microbial polymers for medical application, and biofuel production.
6. High Frequency Graphene Transistors
Typical high frequency transistors are made from Si or more expensive semiconductors such as GaAs or InP. Due to high transit velocity graphene transistors can be 10-100 times faster which will revolutionize the future electronic world. In addition, the transit velocity of charge carriers in graphene is relatively independent of temperature, making it extremely attractive for high frequency and high temperature applications and systems. Moreover, graphene transistors will have low power consumption due to low voltage and the low resistivity of this material. We aim to develop graphene high frequency transistors which are significantly faster, consume less power and cheaper than those made from conventional semiconductors and will be the future dominant RF transistors.
Dr. Yang Hyunsoo is an Assistant Professor at the Department of Electrical and Computer Engineering at the National University of Singapore. He earned his M.S. and Ph.D. degrees in the Electrical Engineering department of Stanford University in 2003 and 2006, respectively. From 1988 he worked at a circuit and system design company, earning a patent award, until 2001, when he enrolled in Stanford's graduate school on a scholarship from the Korean Ministry of Information and Communications. He had been working on long-wavelength photonic devices at Stanford University. From 2004 to 2007 he had been at IBM-Stanford Spintronic Science and Applications Center. He was awarded the fellowship in the conference on Magnetism and Magnetic Materials for 2005 and the American Physical Society (GMAG) outstanding dissertation award for 2006. His recent research focuses on the spintronics, carbon electronics, and solar cells.
7. Creating A Comprehensive Lexical Index of Documents from the World Wide Web (WWW)
We propose to implement the infrastructure necessary to create a database which acts as a lexical index to World Wide Web (WWW) documents and is amenable for extensive semantic analysis. Such an infrastructure consists of two artifacts: (a) a massively parallel crawler capable of efficient on-the-fly lexical analysis of web documents, and (b) a petabyte-scale database system where the crawler writes its output. Our proposed index, as elaborated in the proposal, is lexically and semantically richer that the indexes used by search engines such as Google. It is also required that the logical and physical design properties of the index database allow for simultaneous fast inserts and real-time retrievals.
Anindya Datta, a highly regarded scientist and technological innovator, has a sustained track record of scientific discovery followed by commercialization of these discoveries though successful ventures introducing disruptive innovations. As a scientist, Anindya is widely recognized as having contributed fundamentally to a few of the key ideas in the areas of databases and the internet. In database systems, Anindya’s work has been directly responsible for the creation of an important class of index structures widely available in commercial DBMSs. In the internet space he invented & holds the patent on component-oriented caching and application layer object storage, which are now recognized as core functionalities of any object-oriented application and widely implemented in dynamic web applications. He has published extensively in journals and conferences with over 60 papers to his credit. His papers on internet caching are among the highest cited body of work in that area. Anindya also has a consistent track record of taking his research to the marketplace via highly successful start-up ventures. His work on caching and object storage was commercialized in a venture called Chutney, which he ran and eventually exited via an acquisition by Cisco Systems. His recent work has been in the search domain and some of this work is being commercialized by a venture called Wordster, regarded as a high-potential Web 2.0 company. Anindya’s undergraduate and graduate degrees are from the Indian Institute of Technology (Kharagpur), and University of Maryland (College Park), respectively. Anindya is currently on the faculty of the School of Computing at the National University of Singapore. In the past he has been on the faculty of the University of Arizona, and Georgia Institute of Technology.
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