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9 March 2021, Singapore – Dr Florent Ginhoux, Dr Ng Lai Guan, and Dr Melissa Ng from A*STAR’s Singapore Immunology Network (SIgN), together with collaborators from Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China have found a new subset of gut cells that organise the intestinal stem cell niche, which is important for tissue repair. The study was published in the scientific journal, Nature on 3 March 2021.

These gut cells protect the colon from acute injury via the ROS–MAP3K2–KLF2–RSPO1 axis and hence are termed MAP3K2-regulated intestinal stromal cells (MRISC). Future investigation of MRISCs for their potential roles in restraining intestinal inflammation and pathology as well as their identification in human tissues and how to mobilise them could offer new therapeutic strategies to treat inflammatory bowel disease and colitis-associated colorectal cancer.

Colorectal cancer is cancer of the colon (the main part of the large intestine) and the rectum (the passageway connecting the colon to the anus). It is the top killer in Singapore, affecting more than 1,200 cases each year¹. Inflammatory bowel disease (IBD) can strike at any age, although most sufferers are diagnosed between the ages of 20 and 40 years².

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. A subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs) show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. Their results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.

Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, “The identification of such population of cells that can modulate the gut stem cell niche offers new therapeutical perspectives for gut disorders and we are going to investigate their presence and functions in human tissues.”

Professor Bing Su, Director, Shanghai Institute of Immunology and co-last author of the study added, “Our study also opens new avenues for studying the roles of these stromal cell subsets not only in gastrointestinal system, but also in many other systems for example immune or neuron systems, both in animal models and in human disease settings.”

More information on the study, “MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche” can be found via the team’s published paper in Nature: https://doi.org/10.1038/s41586-021-03283-y

Singapore kicked off its COVID-19 vaccinations for seniors aged 70 and above last week. Professor Lam Kong Peng, executive director of the Singapore Immunology Network (SIgN) under the Agency for Science, Technology and Research (A*STAR), and Dr Zhang Biyan, SIgN immunology research fellow, answered questions on whether there are benefits in receiving the vaccine early, and how important is it for the elderly to get their shots.

Scientists are studying the similarities between long COVID and ongoing symptoms experienced by survivors of Ebola and Chikungunya virus in the hope of devising new treatments to improve their health. Like patients with long COVID, survivors of those other, relatively new human viruses, often experience lingering symptoms which can make it difficult to work or function in everyday life.

Lisa Ng, senior principal investigator at the Singapore Immunology Network (SIgN), has done some studies in people who’ve recovered from Chikungunya virus. She stresses that Chikungunya is very different to COVID-19; although debilitating, it rarely causes severe disease or respiratory syndromes. Ng’s studies suggest T helper cells may be contributing to ongoing inflammation in the joints of people who’ve recovered from Chikungunya. Such insights could lead to potential treatments, such as the repurposing of existing anti-inflammatory drugs, or the development of new immunotherapies for such post-viral syndromes.

About 5 per cent of available vaccine stocks at any point in time should be set aside for people working in areas critical to Singapore's functioning, said the expert committee on COVID-19 vaccination. This was among the key recommendations made by the expert committee, and the Ministry of Health (MOH) said that the government has accepted the committee’s recommendations in full. The expert committee was tasked by MOH in October to devise a vaccine strategy for Singapore. Professor Laurent Renia, executive director and senior principal investigator at the Agency for Science, Technology and Research (A*STAR) Infectious Diseases Laboratories, and Associate Professor Ren Ee Chee, principal investigator at A*STAR’s Singapore Immunology Network (SIgN), are among the members of the committee.

Bacteria and viruses have got smarter, and some diseases seem to be threatening a comeback. With tried and tested defences losing the race against infections, the series Disease Hunters uncovers the novel treatments coming up. 
 
One disease that genetic engineering has shown promise against is dengue. One of the challenges to vaccinate against dengue is that the virus changes shape under different conditions, resulting in four serotypes. 
 
The Agency for Science, Technology and Research’s (A*STAR) Singapore Immunology Network (SIgN) is in the advanced stages of developing an antibody that is effective against all four serotypes of dengue. The antibody attaches to structures on the virus like a “key entering the lock”, said Laurent Renia, the former executive director of SIgN and current executive director of the A*STAR Infectious Diseases Laboratories. This, in turn, triggers the immune system to destroy the virus.

With more than 200 potential Covid-19 vaccines being developed globally, we are inundated each day with news on the latest developments. Covid-19 fuelled the development of an unprecedented number of vaccine platforms, some of which have never before been approved for use in humans. From the outset, it was important to address multiple concerns. In an opinion editorial article, Professors Benjamin Seet and Ren Ee Chee, who are both members of the Ministry of Health's expert committee on Covid-19 vaccination, shared the process and challenges of reviewing more than 40 vaccine candidates over the past seven months.

Professor Ren Ee Chee is an immunologist, and principal investigator at the Singapore Immunology Network (SIgN), under the Agency for Science, Technology and Research (A*STAR), and adjunct associate professor with the Yong Loo Lin School of Medicine at the National University of Singapore.

This ScienceTalk piece about COVID-19 treatments and their role in the war against the pandemic was co-authored by the Experimental Drug Development Centre’s (EDDC) Chief Executive Officer Professor Damian O’Connell, and the National Centre for Infectious Diseases’ (NCID) Associate Professor David Lye.

The article highlights different therapeutic approaches to treating COVID-19, plus global and local efforts to develop therapeutics against COVID-19. In Singapore, A*STAR is collaborating with Chugai Pharmabody Research, a research centre of Japan's Chugai Group in Singapore, on joint research on a therapeutic antibody to fight COVID-19. The project focuses on a potential therapeutic antibody discovered by a research team at A*STAR's Singapore Immunology Network (SIgN), which worked in close collaboration with DSO National Laboratories at their high-containment Biosafety Level-3 facilities. 

Meanwhile, EDDC is supporting several local programmes to address the immediate situation at hand with a mid-to-long term view in mind. Apart from active in-house drug discovery, its programmes include sharing technical know-how on drug development with local players, participating in the national discourse on COVID-19 in several forums, supporting the development of diagnostic assays (particularly the Fortitude Kit for detecting SARS-CoV-2) as well as the clinical translation of novel monocloncal antibodies (mAbs) against SARS-CoV-2 from bench to bedside. 

EDDC’s discovery programme on small molecules focuses on developing a broad-spectrum antiviral drug to counter future novel infectious disease outbreaks, under an accelerated timeframe. EDDC is also supporting local biotech companies – ASLAN pharmaceuticals, AUM Biosciences, and Rhea Pharmaceutical Sciences – to test their compounds as possible treatments for COVID-19.

In addition, EDDC is working with DSO in the pre-clinical and clinical development of a potential COVID-19 therapeutic called AOD01, which is a SARS-CoV-2 neutralising mAb. The safety and pharmacokinetics of AOD01 will be evaluated in healthy subjects during clinical studies in Singapore, followed by looking at the drug's antiviral activity in COVID-19 patients. 

The Ministry of Health (MOH) has appointed a 14-member committee to make recommendations to the Government on its Covid-19 vaccination strategy, and ensure the safe and effective use of vaccines against the coronavirus. The committee's role is to consider the most up-to-date information and assessment of Covid-19 vaccines, including closely monitoring the global vaccine development landscape and stance of agencies such as the World Health Organisation. 
 
Professor Laurent Renia, executive director and senior principal investigator at Infectious Diseases Laboratories, and senior principal investigator at Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), together with Associate Professor Ren Ee Chee, principal investigator at the Singapore Immunology Network, are named as part of the 14-member committee. 

Mothers can pass allergies to offspring while they are developing in the womb, researchers from the Agency for Science, Technology and Research (A*STAR), KK Women's and Children's Hospital (KKH) and Duke-NUS Medical School in Singapore reported in the journal Science on 30 October. 

Currently, there is a significant lack of knowledge on mast cells that are present early on in the developing fetus, notes Florent Ginhoux, study co-author and senior principal investigator at A*STAR's Singapore Immunology Network.

The research, in laboratory studies, also demonstrated that maternal IgE can bind to human fetal mast cells, suggesting that a similar crossover takes place in humans.

The findings open up the possibility of new intervention strategies to prevent allergies being passed from mother to child. "We could identify highly allergic mothers and try to reduce their IgE levels during pregnancy by removing them from blood circulation," Ginhoux tells SciDev.Net.

Scientists from A*STAR’s Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), National Cancer Centre Singapore (NCCS) and KK Women’s and Children’s Hospital (KKH) uncover interactions involved in foetal-like reprogramming of liver cancer cells. By conducting a comparative study that involved mapping 200,000 single human liver cells from foetal development to terminal liver cancer, the researchers discovered two new foetal-associated cell types that were present in the tumour ecosystem of HCC. “Our research underscores a fundamental understanding of how early developmental processes can be hijacked by cancers in order to facilitate their own growth, and escape immune surveillance,” said Dr. Ramanuj DasGupta, the Senior Group Leader at GIS and the lead corresponding author of the study.

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB), in collaboration with doctors from KK Women’s and Children’s Hospital (KKH), have discovered a new immune pathway based on an investigation of severe immunodeficiency caused by a novel mutation in the NFKBIA gene. The findings were published in The Journal of Clinical Investigation. 

Scientists at A*STAR identified a new genetic variant in NFKBIA that changed the levels of soluble proteins called cytokines. Abnormally high production of one cytokine, IL-1β, was identified as the key derangement. In addition, the research team, along with Singapore Immunology Network (SIgN) discovered a previously unknown pathway, which controls IL-1β production. These findings have implications for the development of treatments against liver disease and cancer that target this novel pathway. 

Dr John Connolly, a Research Director at IMCB, said that the mutation found in the study is the only mutation in which hyper-production of IL-1β, severe liver cholestasis and systemic inflammation were documented. He added that the mutation limits immune responses via the suppression of many pro-inflammatory cytokines and causes over-production of IL-1β, leading to liver damage and inflammation. Hence, the use of this bedside-to-bench approach to identify the underlying genetic causes of immunodeficiency diseases, previously unknown pathways which control immune responses can be revealed. These then serve as targets for personalised treatment strategies.

Mothers can pass allergies to offspring while they are developing in the womb, researchers from the Agency for Science, Technology and Research (A*STAR), KK Women's and Children's Hospital (KKH) and Duke-NUS Medical School in Singapore reported this week in the journal Science. The study shows that the key antibody responsible for triggering allergic reactions, immunoglobulin E (IgE), can cross the placenta and enter the fetus. The study findings can potentially open new intervention strategies to limit such transfer to minimize the occurrence of neonatal allergies.

Dr. Florent Ginhoux, senior principal investigator at A*STAR's Singapore Immunology Network (SIgN), said, "There is currently a significant lack of knowledge on mast cells that are present early on in the developing fetus. Here, we discovered that fetal mast cells phenotypically mature through the course of pregnancy, and can be sensitized by IgE of maternal origin that cross the placental barrier. The study suggests that a highly allergic pregnant mother may potentially transfer her IgE to her baby that consequently develop allergic reactions when exposed to the first time to the allergen." 

Researchers from A*STAR’s Singapore Immunology Network (SIgN), together with international collaborators have discovered blood markers that could predict COVID-19 severity and/or risk in patients. The study was published in the scientific journal, Cell on 17 September 2020. The study identified biomarkers (calprotectin) and cellular markers (monocyte and neutrophil subsets) in the blood of COVID-19 patients that could potentially be used as predictors or risk factors of progression from mild to severe forms of the disease. Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, "Our study integrates frequencies of non-classical monocytes and immature neutrophils with calprotectin plasma levels as robust biomarkers of COVID-19 severity and suggests potential therapeutic strategies targeting calprotectin to alleviate severe COVID-19.”

The coronavirus pandemic may have taken much of the world by surprise, but such outbreaks are nothing new. At the frontlines of the age-old battle against disease-causing pathogens are scientists like Professor Lisa Ng, who is a senior principal investigator at the Agency for Science, Technology and Research’s (A*STAR) Singapore Immunology Network (SIgN). Since her days as young biochemistry undergraduate at the University of Manchester Institute of Science and Technology, Ng already had a keen interest in infectious diseases. This led her to pursue a PhD in molecular virology at the National University of Singapore, followed by a postdoctoral stint at A*STAR’s Genome Institute of Singapore. 

Over the next two decades, Ng has grown to play a pivotal role in Singapore’s scientific response to infectious diseases. She was recruited to be part of the A*STAR diagnostic research team during the 2003 SARS epidemic. Along with her colleagues, Ng developed a test that could detect SARS-CoV in patient blood samples. In the following years, she also helped create diagnostic assays for bird flu and Zika, on top of establishing biomarkers for chikungunya.

A team of researchers and clinician-scientists from A*STAR’s Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), National Cancer Centre Singapore (NCCS), and KK Women’s and Children’s Hospital (KKH), have identified a pivotal “fetal-like” reprogramming of the tumour ecosystem in human hepatocellular carcinoma (HCC). The study leveraged the platform established by the National Medical Research Council (NMRC) Translational and Clinical Research (TCR) Flagship Programme in Liver Cancer and was recently published in Cell on 24 September 2020. The team identified the reappearance of fetal-like endothelial cells that are responsible for blood supply, and fetal-like macrophages, an immune cell type that serves as the body’s first line of defence against pathogens, but are also associated with tissue homeostasis.

Researchers from A*STAR’s Singapore Immunology Network (SIgN), together with international collaborators have discovered blood markers that could predict COVID-19 severity and/or risk in patients. The study was published in the scientific journal, Cell on 17 September 2020. The study identified biomarkers (calprotectin) and cellular markers (monocyte and neutrophil subsets) in the blood of COVID-19 patients that could potentially be used as predictors or risk factors of progression from mild to severe forms of the disease. 
 
Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, "Our study integrates frequencies of non-classical monocytes and immature neutrophils with calprotectin plasma levels as robust biomarkers of COVID-19 severity and suggests potential therapeutic strategies targeting calprotectin to alleviate severe COVID-19.”

These 7 SIgN researchers are recognized for their scientific excellence, contributions and influence in their fields through the publication of multiple highly cited papers during the last decade. Heartiest congratulations them!

Dr Chen Jinmiao
Dr Florent Ginhoux (5th consecutive time since 2016)
Dr Ng Lai Guan
Dr Subhra Biswas (2nd consecutive time since 2019)
Dr Anis Larbi (alumni)
Dr Andreas Schlitzer (alumni and 2nd consecutive time since 2019)
Dr Peter See (alumni)

11 September 2020

A team of researchers at A*STAR’s Singapore Immunology Network (SIgN), led by Senior Principal Investigator Wang Cheng-I, has made a tremendous breakthrough in identifying antibodies that block the SARS-CoV-2 virus from entering human cells, thus thwarting the symptoms of COVID-19. The team recently established a partnership with Japanese pharmaceutical company Chugai Pharmabody Research and is currently working at full tilt to bring these antibody candidate drugs to the clinic.

Reported in: Medical Xpress

8 September 2020

A collaborative study among medical professionals and scientists from the National Centre for Infectious Diseases (NCID) and A*STAR’s Singapore Immunology Network (SIgN) unveiled four crucial epitopes on the crown of the SARS-CoV-2 virus to which patient-derived antibodies can bind. Discoveries from two cooperative studies by scientists and medical professionals have been published in Nature Communications and EBioMedicine. The researchers found that patient-derived antibodies can accurately detect these four epitopes – S14P5, S21P2, S20P2 and N4P5 – located on spike proteins of the SARS-CoV-2 virus’ characteristic crown. N4P5 in particular, demonstrated the greatest specificity and sensitivity (100% and >96% respectively) against the SARS-CoV-2 virus.

Reported in: Asia Biotech

24 August 2020

Singapore scientists from A*STAR’s Singapore Immunology Network (SIgN), the National Centre for Infectious Diseases (NCID) and Duke-NUS Medical School have discovered a new variant of the COVID-19 virus that causes milder infections. The study was published in The Lancet medical journal and showed that COVID-19 patients infected with this new variant of SARS-CoV-2 had better clinical outcomes.

The variant, which likely came from Wuhan, China, was detected in a cluster of infections that occurred from January to March 2020. The variant has a large deletion that removes the ORF8 gene. In Singapore, the virus was transmitted from person-to-person across several clusters before being contained. The findings could have implications on the development of treatments and vaccines.

Reported in: Medical Xpress

21 August 2020

Singapore scientists from A*STAR’s Singapore Immunology Network (SIgN), the National Centre for Infectious Diseases (NCID) and Duke-NUS Medical School have discovered a new variant of the COVID-19 virus that causes milder infections. The study was published in The Lancet medical journal and showed that COVID-19 patients infected with this new variant of SARS-CoV-2 had better clinical outcomes.

The variant, which likely came from Wuhan, China, was detected in a cluster of infections that occurred from January to March 2020. The variant has a large deletion that removes the ORF8 gene. In Singapore, the virus was transmitted from person-to-person across several clusters before being contained. The findings could have implications on the development of treatments and vaccines.

Reported in: Reuters

19 August 2020

AUM Biosciences (AUM), a Singapore-headquartered clinical-stage biopharmaceutical company aiming to democratise R&D with a focus on discovering, acquiring, and developing novel therapeutics in oncology, has announced that together with A*STAR’s Singapore Immunology Network (SIgN), a new joint lab will be established in Singapore, centered on drug development and immuno-monitoring of novel oncology drugs. Housed in SIgN’s premises at Biopolis, Singapore’s biomedical research hub, the joint lab will focus on the discovery of novel and proprietary immune biomarkers and underlying drug mechanisms of action that will be used to better inform clinical trial design and study endpoint analysis. Combining SIgN’s scientific expertise in translational immunology, preclinical, and computational research with AUM’s extensive capabilities in clinical trial design and management will lead to better targeted development programmes for AUM’s cancer therapies.

Reported in: Bio Spectrum

18 July 2020

Researchers in Singapore have discovered the specific sites on the novel coronavirus that trigger the body to produce antibodies that can prevent further COVID-19 infection. These findings by scientists from the National Centre for Infectious Diseases (NCID) and the Agency for Science, Technology and Research (A*STAR) demonstrated that antibodies produced during infection attach to many parts of the virus, but only some antibodies are capable of eliminating the virus or offering protection against infection. Whether the antibodies produced are able to counteract the virus after attaching to its surface depends on where exactly they attach, the agencies said. The specific sites are called epitopes.

Professor Lisa Ng, Senior Principal Investigator at A*STAR’s Singapore Immunology Network, said that “the identification of these specific targets on the virus is a crucial advance in the development of better diagnostics and treatments for COVID-19. There is also potential to use these targets against similar coronaviruses to address other viral outbreaks.”

Reported in: Channel News Asia

6 June 2020

An op-ed by Dr Benjamin Seet, group chief research officer for the National Healthcare Group, and Professor Laurent Renia, executive director of A*STAR’s Singapore Immunology Network (SIgN), points out that the race for the Covid-19 vaccine has been elevated to the global stage. We are now witnesses to an interplay between science, biotechnology, public health, markets, governments and civil society. It remains to be seen how the pandemic will evolve, and what role a vaccine will eventually play in bringing it to an end.

Reported in: The Straits Times

28 May 2020

A team of scientists and researchers from A*STAR's Singapore A team of scientists and researchers from A*STAR's Singapore Immunology Network (SIgN) and Jinan University, Guangzhou, have deciphered human embryonic immune cell development and discovered how the earliest macrophages in humans stem from a distinct embryonic source and not the bone marrow. The study was co-led by Senior Principal Investigator Dr Florent Ginhoux from SIgN, as well as Prof Lan Yu and Prof Bing Liu from Jinan University.

Reported in: Asia Research News

23 May 2020

A number of Singapore groups have joined the international race to develop monoclonal antibodies against COVID-19. Monoclonal antibodies are immune system proteins that are created in the laboratory. Those include local biotech company Tychan, as well as a partnership between A*STAR’s Singapore Immunology Network (SIgN) and pharmaceutical company Chugai. Monoclonal antibodies can be specially designed and engineered to target the SARS-CoV-2 virus.

Reported in: The Straits Times

19 May 2020

Researchers at Singapore's Agency for Science, Technology and Research (A*STAR) have discovered an antibody that targets a specific part of the coronavirus, preventing it from infecting human cells, and are moving to develop it to defend against the COVID-19 disease. Dr Wang Cheng-I, senior principal investigator at A*STAR's Singapore Immunology Network (SIgN), said that his team discovered the antibody in mid-March, finding it in a collection of 30 billion human antibodies made by recombinant DNA technology. They confirmed its ability to prevent infection early last month. A*STAR is working on optimising the therapeutic antibody together with Japanese pharmaceutical company Chugai Pharmabody Research, with the aim of engineering it for clinical use. Dr Wang said the two organisations have a history of collaborating on antibody research, including on projects related to dengue.

Reported in: The Straits Times

15 May 2020

A*STAR is collaborating with Chugai Pharmabody Research, a research centre of the Chugai Group in Singapore, on joint research on a therapeutic antibody to fight COVID-19. The project focuses on a potential therapeutic antibody that was discovered by a research team at A*STAR’s Singapore Immunology Network (SIgN), led by Senior Principal Investigator Dr Wang Cheng-I. Professor Sir David Lane, Chief Scientist of A*STAR and Chairman of Chugai Pharmabody Research, explained more about antibodies and their role in treating COVID-19. He shared how the team hopes to develop the antibody that can neutralise the virus, into a medicine that can be given to people. It would potentially be able to treat COVID-19 patients, and even protect those without the disease.

14 May 2020

Dr Lisa Ng, senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN), and a leading infectious disease expert on infection and immunity, shares how her team’s prior experience has helped them quickly understand the nature of SARS-CoV-2, the virus that causes COVID-19. To provide the global scientific community with a roadmap to plan its next steps, she and her team has published their research findings in Nature Reviews Immunology.

Reported in: Medical Xpress

14 May 2020

The article shares how scientists - the detectives of the microbial world - are still learning more about the virus which causes COVID-19, so that tests, drugs and vaccines can be developed to identify and treat those who are infected, and inoculate those who are not.

Viruses are prone to mutations, so Dr Sebastian Maurer-Stroh, deputy executive director for research at A*STAR’s Bioinformatics Institute (BII) is involved in surveillance of the viral genome. He said that the mutations in the coronavirus so far have made little difference in its ability to infect humans.

Scientists are also discovering how the virus can cause disease in the human body and invade human cells. Dr Poh Chek Meng, research fellow at A*STAR's Singapore Immunology Network (SIgN), shared how the SARS-CoV-2 virus could invade lung cells and cause great damage in people who have compromised immune systems, and how the immune system itself could sometimes cause damage too.  Dr Matthew Tay, also a research fellow at A*STAR's SIgN added that an immune system element called cytokines instruct the body's immune 'soldiers' to come to the area and search for pathogens to eliminate.

One of the tools that humanity can use to fight the virus is antibody therapy. Chugai Pharmabody Research Pte. Ltd. (CPR), a research center of the Chugai Group in Singapore, joint research with A*STAR on a therapeutic antibody to fight COVID-19. This antibody targets the S-protein of the virus, preventing it from attaching onto a human host cell.

Reported in: The Straits Times

8 May 2020

Chugai Pharmabody Research Pte. Ltd. (CPR), a research center of the Chugai Group in Singapore, has begun joint research on a therapeutic antibody to fight COVID-19, with the Agency for Science, Technology and Research (A*STAR) in Singapore. This joint research project focuses on a potential therapeutic antibody for COVID-19 that was discovered by a research team led by Senior Principal Investigator Dr Cheng-I Wang at A*STAR’s Singapore Immunology Network (SIgN). Lead candidates were isolated from a high diversity synthetic human antibody library and showed high potency in neutralising live coronavirus which causes COVID-19.

Reported in: Bio Spectrum, Chugai Pharm

4 May 2020

Professor Lisa Ng, Senior Principal Investigator at A*STAR's Singapore Immunology Network (SIgN), outlines different detection methods for viruses such as SARS-CoV-2, including PCR and immunoassays that detect antibodies from individuals. She shares about considerations in the development of such detection methods, and how the results will help to shed light on the epidemiology of novel diseases like COVID-19.

Watch from: Frontiers, Youtube

30 April 2020

The COVID-19 research workgroup, chaired by National Centre for Infectious Diseases (NCID) executive director Leo Yee Sin, commissioned three studies that were released yesterday. The Health Ministry's chief health scientist, Professor Tan Chorh Chuan, is its adviser. The workgroup comprises 18 members from the ministry, public healthcare institutions, the Agency for Science, Technology and Research (A*STAR), and DSO National Laboratories. Among the workgroup are Professors Laurent Renia and Lisa Ng from SIgN, and Dr Sebastian Maurer-Stroh from BII.

Reported in: The Straits Times

6 April 2020

A team of Singapore scientists have found that patients with Covid-19 could have a dynamic and fluctuating immune response to the virus, particularly in the early stages of the disease. The finding is important as it could pave the way for research into existing or new drugs that could help prevent harmful immune reactions that may worsen the disease, said Dr Eugenia Ong, a member of the team and senior research fellow at Duke-NUS’ Emerging Infectious Diseases programme. "The study of very early stages of infection is interesting, and could lead to opportunities for early interventions. Potentially, some clinically approved drugs could be used to target certain inflammatory pathways to control virus-induced inflammation," said Professor Lisa Ng, senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN).

Reported in: The Straits Times, Asia One Online

11 March 2020

Fluidigm Corporation today announced the establishment of a new Center of Excellence (CoE) for Imaging Mass Cytometry™ (IMC™) in Singapore together with A*STAR’s Singapore Immunology Network (SIgN). The center will focus on single-cell deep spatial immunoprofiling to demonstrate the utility of highly multiplexed imaging across a range of disease areas such as cancer immunology. IMC, based on CyTOF® technology, is revolutionizing translational and clinical research by providing unprecedented visualization of complex cellular phenotypes and their relationships in the context of cancer, immuno-oncology, and immune-mediated diseases.

Reported in: Yahoo Online, Bio World, Market Screener, Globe Newswire

25 February 2020

Professor Lisa Ng, senior principal investigator of A*STAR’s Singapore Immunology Network (SIgN), said Sars had served as a “wake-up call” for the Lion City. “For Singapore, the Sars experience was a wake-up call about how diseases know no borders...” But from there, government agencies learned that maintaining a strong working relationship between scientists and the public health community was key, Ng said, adding that this dynamic has been “instrumental” in containing the current outbreak. Dr Sebastian Maurer-Stroh, deputy executive director of A*STAR’s Bioinformatics Institute (BII), said, “There is a good interplay between agencies, as the complementary puzzle pieces create the big picture needed to deal with complexities of an outbreak,” he added. “Coordination is also key and Singapore has just the critical size – not too big and not too small – where this can be done efficiently.”

Reported in: South China Morning Post

18 February 2020

Scientists from A*STAR’s Singapore Immunology Network (SIgN) have discovered that malaria parasites can sense a molecule produced by approaching immune cells and then use it to protect themselves from destruction. The new findings were published in eLife. The study reveals a previously unknown reversible mechanism that malaria uses to evade the immune system, paving the way towards new antimalarial drugs.

Reported in: Science Daily, Medical Xpress, Eureka Alert, Asia Research News

16 February 2020

Scientists around the world are looking to develop a cure for Covid-19. Experts from the Agency for Science, Technology and Research (A*STAR) and Tan Tock Seng Hospital have developed a diagnostic test kit that has been rolled out at a number of public hospitals in Singapore and also delivered to China. Professor Lisa Ng, Senior Principal Investigator at A*STAR's Singapore Immunology Network (SIgN) studies how the virus works and how the human body reacts to it, by analysing samples from patients in Singapore, and by working closely with clinicians and healthcare workers who interact directly with patients.

Reported in: The Straits Times

5 February 2020

Scientists are trying understand the genome of the coronavirus which originated in Wuhan, China. For patients infected with the coronavirus, additional proteins could lead to an inflammation of the lung tissue and cause pneumonia-like symptoms. Professor Lisa Ng, a senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN) said that the infection with viruses sometimes cause exuberant immune responses known as 'cytokine storms'. This means excessive levels of pro-inflammatory cytokines will be produced.

Reported in: The Straits Times

26 November 2019

Scientists from A*STAR’s  Singapore Immunology Network (SIgN) have developed a live-attenuated vaccine candidate against the chikungunya (CHIKV) virus, which causes fever and joint pain in its human host, using targeted mutagenesis. The team introduced missense mutations into the CHIKV genome that were based on naturally occurring mutations in the Semliki Forest virus. Because the Semliki Forest virus belongs to the same family of alphaviruses as CHIKV, her team hypothesized that mutations resulting in less virulent Semliki Forest virus strains would similarly impair the ability of CHIKV to cause infections.

28 October 2019

Researchers at A*STAR’s Institute of Molecular and Cell Biology (IMCB) and Singapore Immunology Network (SIgN), have found a way to strengthen the immune response to adenovirus infection using engineered antibodies. The team focused on how a protein called TRIM21 mediates the immune response to adenoviruses, a class of viruses that can cause conjunctivitis or gastroenteritis, among other health conditions. They focused on TRIM21 because the protein is involved in the degradation of the immune complexes and mediates signaling inside DCs.

Published in: A*STAR Research

25 October 2019

Researchers at A*STAR’s Singapore Immunology Network (SIgN) and Genome Institute of Singapore (GIS) have demonstrated that in HBV-infected patients with the A*11:01 allele, which is more common among East Asians, recovery and long term suppression of HBV was associated with higher frequencies of T cells that target a critical sequence of amino acids in the virus. The findings are highly relevant to patients in Singapore and the Asia Pacific region.

Published in: A*STAR Research

18 September 2019

Researchers from A*STAR’s Singapore Immunology Network (SIgN) have developed a method to obtain a holistic view of the identities and proportions of immune cells in patient blood samples. These findings have gone towards the development of an app for use by the broader scientific community. Moving forward, the group is planning on using single-cell data for the deconvolution of more cell subsets than ever performed.

Published in: A*STAR Research

3 September 2019

Scientists from A*STAR’s Singapore Immunology Network (SIgN) have revealed that different HNF4ɑ isoforms can indeed cross-interact, forming heterodimers. These HNF4ɑ heterodimers control different sets of downstream genes, explaining how a single gene regulator can have such a diverse range of targets. Diseases like colorectal cancer have altered HNF4ɑ2 and HNF4ɑ8 levels and knowing that heterodimerization exists allows the team to investigate which genes are regulated by both homodimerization and heterodimerization of these isoforms.

3 September 2019

Scientists from A*STAR’s Singapore Immunology Network (SIgN) have demonstrated that the loss of Viperin in mice is responsible for a host-damaging immune response to chikungunya virus (CHIKV) infection. The team first showed that CHIKV-infected mice lacking the Viperin gene (Viperin-KO mice) had greater joint swelling than normal mice. Joint swelling was alleviated when the researchers used an antibody to deplete a subset of immune cells - CD4+ T-cells - in Viperin-KO infected mice, showing that CD4+ T-cells were responsible for more severe joint swelling during infection.

Published in: A*STAR Research

3 September 2019

Scientists from A*STAR’s Singapore Immunology Network (SIgN) have identified Zika virus-specific epitopes - short protein sequences on the Zika virus to which antibodies bind - to increase the accuracy of serological testing for the virus. The research was carried out in collaboration with colleagues at the University of Campinas, Brazil, the country at the epicenter of the 2016 pandemic. Beyond facilitating the development of diagnostic tools, the identification of Zika virus-specific epitopes could lead to vaccines against the Zika virus.

Published in: A*STAR Research

28 June 2019

An international team of researchers led by Professor Ido Amit from the Weizmann Institute of Science, Israel with Dr Florent Ginhoux and Dr Camille Blériot from the Singapore Immunology Network (SIgN), A*STAR and Dr Zhaoyuan Liu, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), has revealed a new mechanism protecting from obesity-related metabolic disorder. They have identified a new population of immune cells called Lipid-Associated Macrophages or LAMs localized in the adipose tissue and have shown that these cells protect the organism from obesity-associated damages notably because of the expression of the gene TREM2. These findings may have important implications for the development of LAM/TREM2-targeted immunotherapies for a wide range of metabolic diseases.

Read more in: Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, Lundgren P, Bleriot C, Liu Z, Deczkowska A, Keren-Shaul H, David E Zmora N, Eldar SM, Lubezky N, Shibolet O, Hill DA, Lazar MA, Colonna M, Ginhoux F, Shapiro H, Elinav E, Amit I. Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner. Cell. 2019 Jun 27. [Epub ahead of print]

25 June 2019

In this study published in Nature Immunology, Dr. Regine Dress and Dr. Florent Ginhoux from SIgN resolve the debate about the origin and lineage affiliation of plasmacytoid dendritic cells. They discovered that plasmacytoid dendritic cells exclusively develop from IL7Rα-expressing lymphoid progenitors, rather than myeloid progenitors as previously believed, and should be considered innate lymphoid cells rather than dendritic cells. This novel knowledge of plasmacytoid dendritic cell ontogeny will enhance our understanding of the function of these cells, and their interactions with other immune cells during steady state and the many diseases they are implicated in.

Read more in: Dress RJ, Dutertre CA, Giladi A, Schlitzer A, Low I, Shadan NB, Tay A, Lum J, Kairi MFBM, Hwang YY, Becht E, Cheng Y, Chevrier M, Larbi A, Newell EW, Amit I, Chen J, Ginhoux F. Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage.Nat Immunol. 2019 Jul;20(7):852-864.

21 June 2019

Dr Amit Singhal from SIgN, in collaboration with Prof Hardy Kornfeld (UMASS, Worcester, USA) and Prof Robert Wallis (Aurum Institute, Johannesburg, SA) received an NIH U01 award (USD 2.91m) to conduct a clinical trial of “metformin as a Host-Directed Therapy for TB”. Dr Singhal was the first to propose usefulness of metformin, a diabetic drug, as an adjunct therapy for TB (https://stm.sciencemag.org/content/6/263/263ra159). Since then, number of retrospective clinical studies including his (https://erj.ersjournals.com/content/53/3/1801695.abstract), describing ~ 280,000 individuals treated with metformin for diabetes showed that metformin reduces the risk for TB infection, progression to TB disease, mortality, lung cavitation and relapse, and that it accelerates sputum conversion independent of glycemic control.

09 July 2019

Researchers from A*STAR’s Singapore Immunology Network (SIgN) in collaboration with the Pasteur Institute in France have studied the expression of immune-related genes in O’nyong nyong virus (ONNV) -infected mosquitoes. Led by Dr Guillaume Carissimo (Research Fellow from Prof Lisa Ng's Lab), the team first determined that the ideal moment to collect mRNA from the mosquitos was three days after the insects had been fed a bloodmeal containing ONNV. At this time point, the ‘battle’ between ONNV and the mosquito’s immune system is taking place in the mosquito’s midgut, which allows the team to assess which genes are expressed differently during this critical phase of first contact.

Media Mentions: Science &Technology Research News

03 July 2019

The National Research Foundation (NRF) has awarded SIgN a Shared Infrastructure Support (SIS) grant in March 2019 for five years. The grant will be used to enhance SIgN’s core capabilities in the areas of Flow Cytometry, Multiple Analysis of Proteins (MAP) and Bioinformatics, as well as develop talent to be well-versed with cutting-edge technologies and contribute to impactful scientific research. With this grant, SIgN will be even better-equipped to develop novel assays to expand its repertoire of cutting-edge technologies for higher throughput, greater quality assurance and increased scientific excellence.

Click here for Scientific News Alert.

10 June 2019

The European Asthma, Allergy and Clinical Immunology (EAACI) Congress 2019 offeres 100 scholarships to EAACI Junior Members. Dr Anand Andiappan (SIgN Fellow) was one of the recipients of the scholarship.

Dr Anand Andiappand with EAACI President at the Scholarship Award Ceremony in Lisbon Portugal on 3rd June 2019.

30 April 2019

Visualizing live cells in the brain has been a long standing challenge. In this study, the authors discovered a new probe, CDr20, which allows to track the major brain immune cells called microglia. CD20r only get fluorescent in microglia due to the presence of a protein named Ugt1a7c. The discovery of this fluorogenic probe open new doors for identifying and studying microglia in vivo, especially in the disease context, as microglia is involved in the pathophysiology of numerous brain disorders, including Alzheimer’s Disease.

Read more in: Kim B, Fukuda M, Lee JY, Su D, Sanu S, Silvin A, Khoo ATT, Kwon T, Liu X, Chi W, Liu XG, Choi S, Wan DSY, Park SJ, Kim JS, Ginhoux F, Je HS and Chang YT. Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate. Angew Chem Int Ed Engl. 2019 Apr 30. [Epub ahead of print]

29 April 2019

An international collaboration between the team led by Dr Norman Pavelka (PI, SIgN) and the team headed by Prof Judith Berman (Tel Aviv University, Israel) led to an important discovery at the crossroads of cancer and fungal infections. Using a combination of genetics and experimental evolution, the team found that Candida albicans, the most important fungal pathogen of humans, can rapidly adapt to survive in the presence of certain chemotherapeutic drugs currently used in cancer patients, such as hydroxyurea (HU). The mechanism of survival required alteration in the number of copies of specific chromosomes in the fungus’ genome, a mutation commonly referred to as aneuploidy. Interestingly, the same aneuploidy that allowed C. albicans to survive the HU treatment also conferred increased survival to an unrelated drug – the first-line antifungal drug caspofungin, which if often administered to cancer patients suffering from fungal infections. The team went on to show that mice infected by an HU-adapted strain of C. albicans carrying that particular aneuploidy were refractory to caspofungin treatment. If confirmed in the clinic, these results could have important implications for the management of cancer patients, who are at elevated risk of developing fungal infections because of the immunosuppression resulting from chemotherapy.

Read more in: Yang F, Teoh F, Tan ASM, Cao Y, Pavelka N, Berman J. Aneuploidy enables cross-adaptation to unrelated drugs. Mol Biol Evol. 2019 Apr 27. [Epub ahead of print]

26 April 2019

CHIKV outbreaks are still prevalent, with significant increase in incidences in the last decade. Given the acute and chronic disabilities caused by CHIKV infection, and the associated economic burden, effective preventive measures are urgently needed to halt CHIKV global expansion. However, there is currently no full-length live-attenuated vaccine against CHIKV. In this study, we show that mutations on key sites in CHIKV non-structural proteins could affect infectivity. Consequentially, animals endure milder disease and clear virus rapidly. Importantly, vaccination with attenuated virus induces long-lasting neutralizing antibodies against CHIKV, which protects against subsequent infections. 

Read more in: Chan YH, Teo TH, Utt A, Tan JJ, Amrun SN, Abu Bakar F, Yee WX, Becht E, Lee CY, Lee B, Rajarethinam R, Newell E, Merits A, Carissimo G, Lum FM, Ng LF. Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate. EMBO Mol Med. 2019 Apr 23. [Epub ahead of print]

29 March 2019

Dr Baptiste Janela and Dr Florent Ginhoux, in collaboration with Nestlé Skin Health R&D/ GALDERMA, found that dermal cDC1 control the sustained recruitment and survival of neutrophils through VEGFα secretion in response to cutaneous bacterial infection. Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. In this study, they found that cDC1s, but not cDC2s, regulated the magnitude of the immune response to various types of bacterial infection by controlling neutrophil recruitment, survival, and functions in inflamed skin. Using single-cell mRNA sequencing, they identified a minor subset of activated EpCAM +CD59 +Ly-6D + cDC1s control neutrophil biology via the specific secretion of the cytokine vascular endothelial growth factor α (VEGF-α). Similar observations were made in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation. Such murine/human parallel comparative study at both transcriptomic and cellular levels will aid understanding of human immune response to bacterial infection and more importantly, may facilitate the development of new molecular targets for the treatment of Acne Vulgaris and others bacterial infections.

Read more in: Janela B, Patel AA, Lau MC, Goh CC, Msallam R, Kong WT, Fehlings M, Hubert S, Lum J, Simoni Y, Malleret B, Zolezzi F, Chen J, Poidinger M, Satpathy AT, Briseno C, Wohn C, Malissen B, Murphy KM, Maini AA, Vanhoutte L, Guilliams M, Vial E, Hennequin L, Newell E, Ng LG, Musette P, Yona S, Hacini-Rachinel F, Ginhoux F. A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils. Immunity. 2019 Mar 26. [Epub ahead of print]

15 March 2019

Here, using single-cell mRNA sequencing, Chakarov et al., found that two independent MRTMs populations exist across tissues with specific niche-dependent phenotype and functional programming. 

Their different roles in homeostasis, immune regulation, and fibrosis renders them attractive and separate cellular targets for the therapeutic exploitation of RTM subsets.

Chakarov S, Lim HY, Tan L, Lim SY, See P, Lum J, Zhang XM, Foo S, Nakamizo S, Duan K, Kong WT, Gentek R, Balachander A, Carbajo D, Bleriot C, Malleret B, Tam JKC, Baig S, Shabeer M, Toh SES, Schlitzer A, Larbi A, Marichal T, Malissen B, Chen J, Poidinger M, Kabashima K, Bajenoff M, Ng LG, Angeli V, Ginhoux F. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science. 2019 Mar 15;363(6432).

Click on the following links to access the paper.
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01 March 2019

Immune cells that protect us from infection might also help us see, suggests this new study, led by the group of Dr Daniel Saban in the Duke Eye Center and in collaboration with the group of Florent Ginhoux in SIgN A*STAR.

Their findings revealed that the immune system is actually needed to help nerve cells in the retina respond appropriately for vision. The research team also showed that these same exact immune cells, called microglia, also protect the retina in inherited diseases that cause blindness in mice. This work may lead to a new understanding for the causes of vision loss in such inherited retinal diseases in patients, which affects several million worldwide. Microglia are traditionally thought of in terms of protecting nerves from infection, but scientists are now appreciating that these immune cells also play key roles in supporting the function of nerves even when there is no infection present. Scientists have known for many years that immune cells are in the retina and that their numbers increase in inherited retinal diseases. This increase is also observed in in another type of retinal disease called age-related macular degeneration (AMD) that affects several million people in the U.S. alone. The precise identity of these immune cells in the disease setting was unknown as microglia are easily mistaken for another immune cell type that can come in from the blood, called monocytes. Also unclear in the field is whether these immune cells in retinal disease are part of problem, or rather are perhaps acting in some protective manner against the disease. These questions are important as immune cells accumulate next the critical layer in disease, called the retinal pigmented epithelium. Deterioration of this layer is thought to be a major cause of vision loss in AMD. This study shows that microglia, not monocytes, accumulate next to the retinal pigmented epithelium in murine model of the disease and that microglia actually protect this layer. Since scientists are focused on trying to find out why the retinal pigmented epithelium deteriorates in AMD and how it can be protected to halt disease, these new findings may offer new clues to the field. The next steps will be to understand exactly how microglia protect this layer in disease and whether this system can be used for therapeutic purposes in retinal degenerative diseases. The results of this study were published in the peer-reviewed journal Immunity in March 2019.

Read more in: O'Koren EG, Yu C, Klingeborn M, Wong AYW, Prigge CL, Mathew R, Kalnitsky J, Msallam RA, Silvin A, Kay JN, Bowes Rickman C, Arshavsky VY, Ginhoux F, Merad M, Saban DR. Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration. Immunity. 2019 Feb 26. [Epub ahead of print]

25 February 2019

Dr Florent Ginhoux in collaboration with the laboratory of Dr Sonia Garel, ENS Paris, reported in the journal “Cell” that the microbiome influences prenatal and adult microglia in a sex-specific manner. Microglia, the resident macrophages of the central nervous system, constitute the first line of defense against injury and infections and represent a novel and important cellular target to potentially alleviate and cure brain diseases. The authors found that microbiome changes have a sex- and time-specific impact on microglia: while embryonic male microglia are very sensitive to the absence of microbiome, only female microglia show significant transcriptomic changes in adulthood in the absence of microbiome. Such age-dependent sex-specific differences is crucial as sex-specific modulation of symptoms by the microbiota has been reported in models of several diseases including Parkinson’s disease or type 1 diabetes. Furthermore, irrespective of the underlying mechanisms, the identification of such distinct temporal windows for enhanced microglial alterations in response to long-term environmental challenges is relevant as epidemiological studies show that males are more susceptible to embryonic and early life challenges such as inflammation, leading to an increased risk factor for Autism Spectrum Disorders (ASD) or earlier onset of schizophrenia. Conversely, depression, auto-immune diseases and Multiple Sclerosis, which develop in adolescents or adults, show a higher occurrence rate in females. These results reveal that microglia act as time and sex-dependent responders to environmental challenges, with a potential direct influence on the etiology of the sex bias observed in pathologies associated with microglial dysfunction.

Thion MS, Low D, Silvin A, Chen J, Grisel P, Schulte-Schrepping J, Blecher R, Ulas T, Squarzoni P, Hoeffel G, Coulpier F, Siopi E, David FS, Scholz C, Shihui F, Lum J, Amoyo AA, Larbi A, Poidinger M, Buttgereit A, Lledo PM, Greter M, Chan JKY, Amit I, Beyer M, Schultze JL, Schlitzer A, Pettersson S, Ginhoux F, Garel S. Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner. Cell. 2018 Jan 25;172(3):500-516.e16.