MEDIA RELEASE 21 APRIL 2010

Research in infectious diseases and immunology receive shot in the arm with fresh funding

1. Twelve research projects on infectious diseases and immunology have been awarded grants by A*STAR’s Biomedical Research Council (BMRC) and Singapore Immunology Network (SIgN) this year. Helmed by researchers from local universities, research institutes and hospitals, these projects account for over one-third of the $23 million in grants from BMRC’s 8th General Grant Call and SIgN’s 4th Grant Call aimed at supporting the translation of lab discoveries to potential clinical therapies for diseases prevalent in Singapore and the region.

Of viral infections and the human immune response

2. Eight projects will examine viral infections and the human immune response. The results of which will potentially lead to better vaccines and improved clinical care for patients. One of the projects is led by Assistant Prof Toh Chee Seng of the National University of Singapore (NUS), who, in close collaboration with dengue and antibody research experts from A*STAR’s SIgN, is developing an ultra-sensitive, low cost biosensor probe system for fast detection of the dengue1 virus. The system comprises a channel of nanometre-scale attached with antibodies that can bind and distinguish between the four serotypes of the dengue virus, as well as a detector.

3. “With this system, we will be able to sense low amounts of the dengue virus in patients’ blood samples, and thus reduce the time needed for analysis from the current six hours to less than one hour. If successful, this system may also be further applied to rapid detection of multiple diseases at clinics, schools and offices during large-scale outbreaks of infectious diseases,” said Assistant Prof Toh.

4. Another project led by Dr Justin Chu from NUS is seeking to answer important questions on the pathogenesis of the chikungunya virus, particularly about how its receptors function and how it enters cells. “This mosquito-borne virus was

1 Dengue fever, together with the associated dengue haemorrhagic fever, is endemic throughout

tropical countries including Singapore, and is the world’s fastest growing vector-borne disease. Globally, there are an estimated 100 million cases of dengue fever annually, 250,000 cases of dengue haemorrhagic fever and an annual mortality rate of 25,000. In Singapore, swift implementation of vector control measures brought the disease, which had caused an epidemic in the 1960s, under control. However, after a lapse of 3 decades, dengue returned to Singapore in the 1990s. Close to 15,000 cases and 25 dengue deaths were reported during an outbreak in 2005.

responsible for a local outbreak in 2008 and is fast becoming a global threat,” said Dr Chu. “It is therefore critical for scientists to develop a good understanding of the complex virus-host interactions, so as to provide the basis for the development of possible therapeutics or vaccines against related viral infections. We hope that our research will ultimately contribute towards better diagnosis and treatment for patients,” he added.

5. The research project on anterior uveitis, a specific form of inflammation of the eye for which the cause remains unknown, is led by Associate Prof Chee Soon Phaik from the Singapore National Eye Centre, in collaboration with Dr Subhra Biswas from SIgN. The team will study the role of the cytomegalovirus (CMV) in anterior uveitis and other eye diseases. CMV, which can infect people of all ages, sexes and ethnic backgrounds, can remain in the body after infection and be reactivated upon subsequent stress to the immune system. It can also be transmitted from mother to baby. Said Assoc Prof Chee, “We have made some early breakthroughs in research on CMV-associated uveitis. Building upon these earlier findings, we aim to use the current research to contribute to improved diagnosis and better management of the disease.”

6. Prof Sir George Radda, Chairman of BMRC, said, “BMRC's General Grant Call provides funding to the most promising of grant applications, which aim to unveil new knowledge, create breakthroughs in biomedical science, and advance translational and clinical research. Funding such research is core to A*STAR's mission and purpose to create industrial advances, economic benefits and better health for all. We are pleased with the quality of the 2009 applications and hope that the scientific community in Singapore will continue to work together to pursue high-impact and meaningful outcomes for society.”

7. Said Prof Paola Castagnoli, Scientific Director of SIgN, “The 2009 SIgN grants were awarded to deserving clinical researchers who, in addition to having original ideas for addressing fundamental clinical problems, demonstrate strong partnerships with scientists who could share relevant skills and knowledge to fulfill common research goals. As Singapore ramps up its efforts in bench-to-bedside translational research, SIgN will continue to contribute to the vibrant research environment here by encouraging the exchange of ideas and expertise between academic, industrial and clinical partners.”

Minding heart and mental health

8. In addition to the research projects on infectious diseases and immunology, grants were also awarded by BMRC to novel research in neuroscience and cardiovascular disease, which could be applied to address pressing health issues in Singapore such as heart disease2 and depression3. A total of 30 projects (a list of 2 Worldwide, 7.2 million or 12.2% of the population die from coronary heart disease each year, a

figure that the World Health Organisation (WHO) expects to increase, especially in the Southeast Asian region. According to the Singapore Heart Foundation, death from cardiovascular disease (including heart disease and stroke) accounted for 32.5% or one in three of all deaths in Singapore, and was second only to cancer.

3 Depression is a serious and debilitating disorder affecting up to 8% of the population in Singapore

and worldwide. Currently available treatments often have significant side-effects, and not all patients

respond to therapy.

the projects is provided in the Annex A) were awarded grants under BMRC’s 8th General Grant Call and SIgN’s 2009 Collaborative Grant Call.

Background

9. Since its inaugural General Grant Call in 2001, BMRC has awarded a total of 414 grants (amounting to over $306 million) to local research institutes and hospitals including NNI, NUS, NTU, Duke-NUS GMS, NUH and NCCS to realise the vision of developing Singapore as a leading hub of biomedical research and development. The 9th BMRC General Grant Call is expected to open for applications on 3 May this year. SIgN has awarded grants to support 26 projects in the field of immunology since its inception in 2006. The SIgN 5th Grant Call is expected to open for applications in July this year.

___________________________________________________________________ Agency for Science, Technology and Research (A*STAR) For media queries, please contact: Wang Yunshi Corporate Communications Agency for Science, Technology and Research (A*STAR) DID: +65 6826 6443 Email: wang_yunshi@a-star.edu.sg

About the Agency for Science, Technology and Research (A*STAR)

A*STAR is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and nine consortia & centres, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity.

A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.

A*STAR’s Biomedical Research Council (BMRC) oversees the development of core research capabilities within A*STAR research units specialising in bioprocessing; chemical synthesis; genomics and proteomics; molecular and cell biology; bioengineering and nanotechnology and computational biology. Through competitive grants, the Council also supports research in the wider scientific community such as public universities and hospitals. As part of its efforts to advance human healthcare, BMRC actively promotes translational medicine and cross-disciplinary research. The Council also engages in human capital development in the biomedical sciences and promotes societal awareness of biomedical research through outreach programmes.

For more information on A*STAR, please visit www.a-star.edu.sg.

About the Singapore Immunology Network (SIgN)

SIgN, officially inaugurated on 15 January 2008, is a research consortium under A*STAR's Biomedical Research Council. It is aimed at building on the strengths of the existing immunology research groups at A*STAR, as well as expanding and strengthening the immunology research expertise in Singapore. SIgN's objectives include coordinating basic, translational and clinical research needed to establish immunology as a core capability in Singapore. The major focus areas of research at SIgN are Infection and Inflammation, in which SIgN researchers investigate immune responses and regulation in disease-specific contexts. Through this, SIgN aims to build up a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local initiatives within Biopolis and across Singapore, as well as to obtain international recognition as a leading immunology research hub while establishing relationships with the best institutions in the world.

For more information about SIgN, please visit www.sign.a-star.edu.sg.

ANNEX A

LIST OF PROJECTS AWARDED

8th BMRC General Grant Call

S/N Project Title Principal

Investigator (PI)

Host

Institution

1 Development of andrographolide and its

derivatives for the treatment of allergic

asthma and asthma exacerbation

Wai Shiu Fred

Wong

NUS

2 Molecular characterization of cellular

receptor(s) and viral attachment domain of

Chikungunya virus: possible implications for

anti-viral therapy and vaccine development

Justin Chu Jang

Hann

NUS

3 Intrauterine gene therapy of haemophilia in a

non-human primate model

Jerry Chan NUS

4 Neurodegeneration in apolipoprotein E4

carriers: The regulation of mTOR1 by labile

zinc as a new mechanism of action

Barry Halliwell NUS

5 Discovering inhibitors against the Dengue

virus NS3 helicase and NS5 polymerase

using a fragment-based approach aided by

X-ray crystallography, N.M.R. and Surface

Plasmon resonance

Julien Lescar NTU

6 Virus-induced host cubic membranes: a novel

biomarker and target for understanding and

combating viral infections

Deng Yuru NUS

7 Functionalization of bioresorbable poly-

epsilon-caprolactone -20% tricalcium

phosphate cage devices to enhance delivery

of biological factors in interbody spine fusion

Wong Hee Kit NUS

8 New insight into liver fibrosis and hepatic

steatosis through label-free imaging using

multimodal nonlinear microscopy imaging

and Raman microspectroscopy at the

molecular and cellular levels

Huang Zhiwei NUS

9 A study to investigate the activation of a new

Akt/NHE-1 feedback loop in the redox

regulation of survival in normal and tumour

cells.

Marie-Veronique

Clement

NUS

10 Studies on the role of peptidyl-prolyl

isomerase Pin1 in regulating TR3-mediated

cell proliferation

Liou Yih Cherng NUS

11 Population coding in the primary visual cortex Yen Shih Cheng NUS

12 Elucidating specificity of BCH domains by

structural and functional characterization of

their complexes with RhoA and glutaminase

Sivaraman

Jayaraman

NUS

13 Ablation of alternatively spliced exon 33 of

Cav1.2 channel by genetic targeting in

mouse: implications in functions of

cardiovascular and nervous systems

Soong Tuck Wah NUS

14 Investigating the isoform-specific effects of

apolipoprotein E on N-methyl-D-aspartate

receptor (NMDAR) signalling during age-

related memory decline.

Wong Boon Seng NUS

15 Understanding the structure and assembly of

subunits E, F, G and a of nature’s most

versatile pump, V-ATPase

Gerhard Grüber NTU

16 An age-related neurodegeneration model in

Drosophila: establishment of links to lipid

metabolism and autophagy, and analysis of

lipidomic changes in sphingolipid and

cholesterol accumulation and trafficking

Rachel Kraut NTU

17 Exploring Wnt regulation in glioma-initiating

cells, and Wnt inhibition as a therapeutic

strategy

Carol Tang NNI

18 Mutation-resistant Antivirals James P. Tam NTU

19 Functional and structural characterization of

functional domains of the Reticulocyte

Binding Proteins of Plasmodium during

merozoite invasion

Peter Rainer

Preiser

NTU

20 Exploration of nuclear proteome for

chromatin remodelling proteins in the human

malaria parasites, Plasmodium falciparum

Zbynek Bozdech NTU

21 Interactions between stress and the serotonin

system in depression

Zhang Xiaodong Duke-NUS-

GMS

22 Genetic Markers of Retinal Vascular Calibre

and Cardiovascular Disease: The Singapore

Malay Eye Study & The Singapore

Prospective Study Programme

Wong Tien Yin SERI

23 Development and spatial expressions of

NR3B subunit in rat brain and functional

properties of Nr3B-containing N-methyl-D-

aspartate receptors

Low Chian-Ming NUS

24 Role of micoRNA in gastric cancer Richie Soong NUS

25 Revealing the structure and function of Orai1

and Stim1: the cause of severe combined

immune deficiency (SCID) syndrome

Said Eshaghi NTU

SIgN 2009 Collaborative Grant Call

S/N Project Title Extramural PI SIgN PI

1

Analysing the roles of CD137

ligand in macrophage polarisation and

myeloid leukemias

Herbert Schwarz

(NUS)

Philippe Kourilsky, Wong Siew Cheng

2

Development of fast response, sensitive

and selective biosensor probe system for

dengue and its serotypes for use at point-

of-cares in Singapore

Chee-Seng Toh

(NUS) Wang Cheng-I, Katja Fink

3

Understanding the innate immune

mechanism mediating human idiopathic

uveitis

Chee Soon Phaik

(Singapore

National Eye

Centre)

Subhra Biswas

4

Longitudinal analysis of the humoral

immune response of dengue patients from

the acute phase up to one year after

infection

Adrian Ong (Tan

Tock Seng

Hospital) Katja Fink