News : SICS launches 2nd Grant Call!
The Singapore Institute for Clinical Sciences (SICS) is announcing a grant call for research proposals in the area of Human Nutritional Science. Proposed research should either directly involve humans, or make use of human samples linked to human phenotype data. Studies solely focused on animal models or on in vitro models using human cell lines not linked to phenotypic data will not be considered responsive to this grant call.
All investigators who hold a primary appointment in a Singapore public institution (including restructured hospitals, national centres, research institutes, local universities and government agencies like Health Promotion Board) are eligible to apply. There should only be one Principal Investigator (PI) who will be responsible for coordinating any team effort and managing the grant award. The research must be conducted in Singapore.
Researchers from overseas institutions and private biotechnology companies can participate as collaborators. However, the terms of collaboration with overseas research institutions and private biotechnology companies must conform to BMRC’s prevailing policies.
Closing date 1 October 2009, 5:00pm.
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Mon, 25 May 2009
News : Immunotherapy: Arming the body against liver cancer
STIMULATING the immune system against the development of tumor cells could be a useful strategy to delay or prevent the onset of liver cancer in chronic hepatitis B patients, according to a recent A*STAR-funded study1. Writing in Gastroenterology, researchers from the Singapore Institute for Clinical Research and other institutes based in Singapore describe their discovery that most patients, even those whose infection has progressed to cancer, have immune T cells that respond to tumor cells. While this could be used to bolster resistance to the development of new tumors, T-cell exhaustion inhibited the response in those who already have liver cancer, the researchers found.
Chronic infection with hepatitis B virus (Fig. 1) is a significant risk factor for the development of the liver cancer known as hepatocellular carcinoma (HCC). Over time, chronic infection typically leads to liver cirrhosis, which develops into HCC in about 80% of patients. This is of particular concern in parts of Asia where hepatitis B virus infection rates are greater than 1 in 10.
There has been limited success in treating HCC using chemotherapy, and removal of the damaged parts of the liver is usually not viable. This leaves only full transplantation as a treatment option. Researchers from A*STAR, the National University of Singapore and Gleneagles Hospital, led by Antonio Bertoletti, studied the possibility of immunotherapy-turning the body's immune system against the tumor cells.
The researchers tested the response of HLA-A2-a type of T cell widespread in Asian and Caucasian populations-to tumor antigens and hepatitis B virus proteins. The T cells were from 30 hepatitis B-infected patients, 10 of whom also had cirrhosis while another 10 had HCC.
T cells from most patients responded to tumor antigens, and some to more than one type of antigen, whereas very few patients responded to the viral proteins. The most active tumor antigens were able to stimulate a full-blown immune reaction. In the cancer patients, however, there was evidence of T-cell exhaustion.
In the livers and tumors of the HCC patients, the researchers observed higher than normal levels of T cells associated with programmed cell death, leading to the speculation that their presence could promote T-cell exhaustion. Blocking active proteins associated with programmed death could perhaps rescue T-cell function, the researchers suggest.
Having demonstrated that T cells can be stimulated to respond against tumor cells in patients with cirrhosis, the researchers believe that in the future it may be possible to target tumor cells in a prophylactic manner to prevent or delay progression to HCC.
- Gehring, A.J., Ho, Z.Z., Tan, A.T., Aung, M.O., Lee, K.H., Tan, K.C., Lim, S.G., Bertoletti, A. Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus-related hepatocellular carcinoma. Gastroenterology published online 27 April 2009 (doi: 10.1053/j.gastro.2009.04.045).
Fri, 24 Apr 2009
News : Local researchers explore new approaches to takle age-old ailments
A*STAR issued research grants for more than 50 biomedical projects on disorders of the immune system, infectious diseases, ageing and cancer.
1. A*STAR's Biomedical Research Council (BMRC) and its consortia, namely Singapore Bioimaging Consortium (SBIC), Singapore Immunology Network (SIgN), Singapore Institute for Clinical Sciences (SICS) and Singapore Stem Cell Consortium (SSCC), have issued more than 50 grants amounting to $36 million to research groups from local universities, research institutes and hospitals this year. The research projects awarded under BMRC's 7th General Grant Call, SBIC-SIgN Joint Grant Call, SSCC Grant Call and SIgN Grant Call, will potentially develop therapeutics for the treatment of ailments of the immune system, infectious diseases, ageing, cancer, etc.
Targeting ailments of the immune system
2. About 20% of the proposals are concerned with the study of what irritates the immune system and causes problems such as allergy, eczema and asthma1. Championing immune health is Prof Chua Kaw Yan of NUS2, who was awarded a record three grants under BMRC's 7th General Grant Call. She will focus on combating the common dust mite, Blomia tropicalis, which is responsible for 60-70% of allergy cases here including asthma, allergic rhinitis and eczema. The first grant will investigate the mechanisms of an oral vaccine against the predominant allergen in B. tropicalis, Blo t 5 protein. Another will focus on optimising the potency of a genetic vaccine, while the third will involve creating a modified or ‘recombinant' protein to foster immunity against Blo t 5.
3. Increased prevalence of allergy is a major global problem and a preventive vaccine is currently unavailable. Said Prof Chua, "Immunotherapy remains the only truly disease-modifying treatment for asthma and allergic rhinitis. Traditional forms of immunotherapy use natural sources of allergens and have numerous disadvantages, such as the presence of undefined material, huge variability in sample composition, and contamination of allergens from other sources. We therefore hope to use the major allergen, Blo t 5, to develop a novel and effective therapeutic vaccine for immunotherapy."
Strategic steps to curb infectious disease
4. Grants have also been awarded to research teams that will use various approaches including genomics, proteomics and bioimaging to study various mechanisms of infection 3 , such as tuberculosis and malaria.
5. The research team led by Dr Ann Lee of the National Cancer Centre of Singapore (NCCS)4 is a case in point. Awarded a BMRC grant, the team will confront Mycobacterium tuberculosis (MTB)5 by sifting through a bank of DNA samples extracted from drug-resistant MTB strains to identify novel mutated genes conferring resistance to Isoniazid, the main drug that combats tuberculosis. Said Dr Lee, "The identification of additional genes associated with Isoniazid resistance is important for the development of comprehensive molecular strategies that are potentially more efficient than current susceptibility testing methods, and could aid in giving more appropriate treatment to patients and decrease the spread of resistant strains. In addition, the discovery of new genes may reveal novel targets suitable for the development of alternative therapeutic options."
6. Another team, led by A/Prof Peter Preiser of Nanyang Technological University (NTU), has been awarded a grant under the SBIC-SIgN Joint Grant Call to conduct basic research on the pathology of malaria. Prof Preiser said, "A key challenge to successful malaria intervention is our limited understanding of how the malarial parasite evades detection by the spleen - our immune system's control centre. With this grant, we will use new imaging tools to visualise and measure how many parasites are eliminated in the spleen. This work will give us a better understanding on which factors, both from the host as well as the parasite, contribute to the efficiency of parasite removal and could lead to new intervention strategies against the parasite."
Tackling problems associated with ageing
7. Also receiving funding are projects that will explore health problems associated with ageing such as neurodegenerative diseases like Alzheimer's and Parkinson's. One of them is Dr Gavin Dawe's group at NUS7, which received a grant under the SSCC Grant Call to explore the signaling mechanisms behind Alzheimer's disease. The grant is a nod to his group's discovery of an important protein interaction that suppresses neural cell formation in the brains of mice, which might have implications for Alzheimer's, the most common form of dementia among older people. Said Dr Dawe, "In this project, we will investigate whether this protein interaction also occurs in human stem cells and in the adult mouse brain, as well as how it influences stem cell function. Our findings will increase our understanding of what these proteins do in the brain and in the long term, this knowledge may contribute to the development of treatments for Alzheimer's disease."
Exploring ways to deal with cancer pathways
8. At least one-fifth of all the grants have been awarded to projects dealing with cancer pathways or working on cancer cell lines. One of the groups led by Prof Shazib Pervaiz of NUS8 has been awarded the BMRC grant to examine how statins - cholesterol-lowering drugs - have the intriguing additional effect of restricting growth and inducing death of cancer cells. This will potentially benefit breast cancer patients. Said Prof Pervaiz, "Current breast cancer therapies include surgery, anti-cancer drugs and radiation, which are invasive or run the risk of relapse. Our team aims to characterise the interactions of statins with other proteins known to promote cell death and survival, and subsequently explore the potential for statins to fill the gap in novel strategies for more effective and less invasive treatment of breast and
other forms of cancer."
Continuing A*STAR's efforts in R&D
9. Said Prof Sir George Radda, Chairman of BMRC, "The grant calls underscore A*STAR's commitment to foster excellent scientific research and talent in Singapore. The wide range of research areas covered under the grant calls is indicative of the spectrum of biomedical capabilities we have built up in Singapore over the years, as well as the high quality of our researchers. I look forward to the exciting and innovative discoveries that will result from the research the scientists are able to carry out with the funding from A*STAR."
10. Since its inaugural General Grant Call in 2001, BMRC has awarded a total of 389 grants (amounting to $285.5 mil) to local research institutes and hospitals including NUS, NUH and NCCS to realise the vision of Singapore becoming a premier centre for biomedical research and development. The 8th BMRC General Grant Call is expected to open for applications on 4 May this year.
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Sat, 28 Feb 2009
News : S'pore zooms in on cancer stem cells
Scientists here seek ways to combat growth of brain tumours
SCIENTISTS here are edging closer to developing drugs to treat aggressive brain tumours by homing in on the special cells which cause them.
These cancer stem cells are responsible for the tumour's wild growth because they can generate new cancer cells. They are also resistant to conventional cancer treatments such as radiotherapy and chemotherapy.
The National Neuroscience Institute (NNI) and Singapore Institute for Clinical Sciences (SICS) have built up a bank of these rare cells by collecting samples from eight patients, with their consent. They are working with the Lilly Singapore Centre for Drug Discovery to study the cells.
In the next 18 months, they hope to pin down what makes them so potent and find out how to kill them.
Such tumours are uncommon, and the survival rate of patients is dismal.
Even after operations to remove the tumour, chemotherapy and radiation, patients live on for only a year more because the cancerous stem cells cause the tumours to grow back.
Dr Carol Tang, head of NNI's Neuro-Oncology Research Laboratory, and Dr Christopher Ang, an NNI neurosurgeon, who are leading the effort, found a way to store these cancer stem cells. Through cryopreservation, a technique similar to that used to preserve eggs during in-vitro fertilisation, they have been able to build a stock of these cells for study.
'It is critical that the brain tumour stem cells do not become altered following storage and our team has described a technique where their character is preserved,' said Dr Ang.
Cancer stem cells divide continuously, causing the growth of tumours.
Dr Ang, who is also a clinical investigator at SICS, said the first step to stopping these cells would be to uncover their genetic make-up.
Researchers from the Lilly centre - opened by pharmaceutical giant Eli Lilly and the largest lab of its kind here - will then try to find a drug to work against them, an effort led by chief scientific officer Jonathon Sedgwick.
Doctors here are excited by the potential of the study.
Dr Daniel Chan, associate consultant at the haemotology-oncology department in the National University Cancer Institute, said that if a new drug could do the trick without the need for extensive surgery or radiotherapy, this would 'lead to a significant improvement in the patient's quality of life'.
The researchers hope their work can be extended to other cancers. Dr Ang said: 'What we may discover in research into brain tumour stem cells could potentially be extrapolated to cancer stem cells responsible for the formation of other tumours.'
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Tue, 17 Feb 2009
News : Public and Private Research Organisations Team Up to Advance Drug Discovery Using Brain Tumour Stem Cells
Lilly Singapore Centre for Drug Discovery (LSCDD), the National Neuroscience Institute (NNI), one of the institutions of SingHealth, the largest public healthcare group in Singapore and the Singapore Institute for Clinical Sciences (SICS) of A*STAR, have teamed up to advance drug discovery using adult brain tumour stem cells. LSCDD, a wholly owned subsidiary of the US-based biopharmaceutical company, Eli Lilly and Company has recently expanded its facility at the Biopolis, and has cancer as one of its disease areas of focus.
The research collaboration will leverage earlier findings by Dr. Carol Tang, a NNI research scientist and Dr. Christopher Ang Beng Ti, a neurosurgeon at NNI and clinical investigator with SICS. The duo have shown that primary brain tumours are caused by a minority group of cells that display a genetic profile distinct from that of the tumour bulk. They have reliably established a method of cryopreservation for
these tumour-initiating cells (frequently termed "cancer stem cells"), thus facilitating the development of a brain tumour stem cell repository for future research and drug screening efforts. These important discoveries were published late last year in the Journal Stem Cells, which reports new findings in this research area.
"Our scientific goals are to understand if and how we can target adult brain tumour stem cells selectively, and to use bioinformatics to identify novel biomarkers and new drug targets", said Dr. Tang and Dr. Ang. "Ultimately, this could lead to new approaches to treat brain tumours."
The researchers have reason to be optimistic. This collaboration is the first amongst staff from Eli Lilly and Company and lead local research agencies, NNI and A*STAR. With increased opportunities for exchanging ideas and synergising efforts, more effective and less invasive cancer treatment is now one step closer to becoming a reality.
Dr. Jonathon D. Sedgwick, Managing Director and Chief Scientific Officer of LSCDD highlighted that "discovering new, breakthrough medicines through translational and clinical research requires intensive collaborations amongst partners. This research collaboration with clinicians and scientists from NNI and SICS will bring together different expertise and resources. This fits well with Lilly's new collaborative model known as the Fully Integrated Pharmaceutical Network (FIPNet) model, and will enhance and accelerate Lilly's ability to find ‘Answers That Matter'."
Prof. Judith Swain, Executive Director of SICS mentioned that "this collaboration is aligned with our focus on disease-oriented clinical and translational research. The family of clinician scientists here at SICS is well-positioned to perform critical work at the border between basic and clinical research. We look forward to working closely with LSCDD and NNI to develop cutting-edge approaches for novel drug development."
"NNI's research aims to improve treatment and discover cures for neurological disease. This collaboration will enable all parties to benefit from the exchange of multidisciplinary expertise and will expedite the translation of research findings into clinical practice", said Prof. Lee Wei Ling, Executive Director of NNI.