In brief

Commemorating 30 years of A*STAR's excellence.

© A*STAR Research

Three decades of driving dedicated research

7 Dec 2021

Through the years, A*STAR has always stood at the forefront of science and technology and innovation. Here’s how A*STAR came to be and what it has in store in the upcoming decades.

Despite being a small island nation with little natural resources, within a generation, Singapore overcame this limitation by steadily investing in its people and their ability to drive research and development (R&D). While early technological advances helped the country establish basic services and a nascent industrial manufacturing sector, science and technology (S&T) research has since transitioned from a survival tool to a crucial economic engine.

Today, the city-state is a prominent international hub for banking, data science, biomedical engineering and innovation. In line with its record of triumphing over adversity, Singapore remains committed to investing in R&D to continue driving the country forward.

With over 30 Research Institutes (RIs) and entities, A*STAR—Singapore’s lead public sector R&D agency—now carries out research across a span of disciplines, from machine learning to manufacturing, photonics to therapeutics and everything in between. Collectively, these efforts have put Singapore on the global science map.

Through its research, A*STAR continues to enhance the lives of those who have made the ‘Little Red Dot’ home. With A*STAR celebrating 30 years of excellence, we revisit the agency’s key milestones and triumphs—and look at how it will continue shaping the nation’s buzzing scientific ecosystem in the years to come.

The seeds of scientific success

Considering that Singapore’s scientific journey only started a little over 50 years ago, the country’s meteoric rise from sleepy fishing village to innovation powerhouse is even more remarkable.

It was in 1967—two years after the Republic’s ‘birth’ in 1965—that the first-ever Science Council was established with Kum Tatt Lee, one of Singapore’s earliest homegrown PhD researchers, at the helm as inaugural Chairman. By bridging industries and training institutes with the government, the Science Council was intended to drive an integrated approach to S&T education.

In 1969, Lee concurrently served as Chairman of the Singapore Institute of Standards and Industrial Research—now the National Metrology Centre (NMC)—to ensure that investments in education would lead to practical output. Likewise recognizing that R&D would be a key economic engine, the Economic Development Board (EDB) started introducing initiatives in the 1970s to attract technology companies to Singapore’s sunny shores.

These efforts proved to be the genesis of the country’s now well-established manufacturing and electronics industry, with industry behemoths like data storage company Seagate flocking to the country in the 1980s. By 1981, the earliest inception of what is now known as the Institute for Infocomm Research (I2R) was launched through the then-Institute of Systems Science, while in 1985, the Singapore Institute of Manufacturing Technology (SIMTech) was set up as the Grumman International/Nanyang Technological Institute (NTI) CAD (Computer-Aided Design)/CAM (Computer-Aided Manufacturing) (GINTIC).

On the other side of the coin, it was also in the 1980s that the local biomedical industry started coming to life. The idea of the Institute of Molecular and Cell Biology (IMCB) was seeded in 1982 when renowned cell biologist Chris Y.H. Tan visited Goh Keng Swee, then-Deputy Prime Minister, presenting an opportunity for Singapore to enter the exciting world of biological discovery.

The agreed strategy was to build IMCB with 12 to 24 research groups to grow science in Asia. In 1983, Sydney Brenner—best known for his Nobel Prize-winning research deciphering the genetic regulation of animal development and programmed cell death through the nematode worm—arrived in Singapore to give a lecture outlining the biotechnology industry. Just before leaving, Brenner met with then-Prime Minister Lee Kuan Yew and further crystallized the idea of setting up IMCB.

Three years later, IMCB was finally launched with Tan as Founding Director and Brenner as Chairman of the advisory board. “I fought hard to recruit the most promising young scientists to Singapore,” recalled Tan. “The time had come to take on the world’s top labs; my confidence in the diversity of talents in Asia drove me.”

Within five years Singapore had made its mark: Science claimed that IMCB had put Singapore on the scientific map1. John Maddox, then-editor at Nature, proclaimed that IMCB had done excellently.

Tan’s work on interferon (IFN) gene regulation and the genetics of IFN action influenced IMCB’s initial research directions. “Cells make IFN to instruct their own cells as well as other cells to stop any virus entering the cell from multiplying,” he explained.

Under his leadership, IMCB researchers found that within hours of exposure to IFN or inflammatory cytokines, the host transforms into an altered state of heightened innate immunity and inflammation2.

Proving the relevance of their findings even decades after, an imbalance of this altered state has since been associated with the severity of coronavirus pathology observed during the 2003 SARS epidemic and the current COVID-19 pandemic.

IMCB later cemented its credibility through major industry-academia R&D collaborations in neuronal cell signaling pathways with what is now known as GlaxoSmithKline (GSK). The institute also collaborated with GSK to use cell signaling targets in discovering new drugs. Following IMCB’s success, it became clear by the late 1990s that for the Republic to further progress, even the manufacturing sector had to undertake R&D. Only then could Singapore move away from mere product assembly and excel in the creation of new technologies.

These ambitions spurred the establishment of A*STAR’s direct predecessor, the National Science and Technology Board (NSTB), on January 11, 1991. At the same time, Singapore’s first five-year National Technology Plan (NTP), with a budget of S$2 billion, was launched to guide the development of Singapore’s fledgling S&T ecosystem.

Transformative growth and development

With the NSTB in place, the nation’s next priority was to attract more corporate players to set up both local R&D and pilot production operations—shortening the time needed to bring products to market. While experienced talent was in short supply then, Singapore’s key location made it a potential gateway to Asia.

As the first step to achieving this lofty goal, NSTB established several industry-oriented RIs. Take for instance the Institute of Microelectronics (IME), which was created to support Singapore’s growing semiconductor industry. Other electronics and manufacturing RIs addressing real-world industry issues also originated in the 1990s, including the former Data Storage Institute (DSI) in 1992, the GINTIC Institute of Manufacturing Technology (GIMT) in 1993 as well as the Institute of High Performance Computing (IHPC) in 1998.

Much like IMCB before them, these institutes started making waves in the scientific world almost immediately. With Singapore’s emerging strength in manufacturing, researchers from GIMT—renamed SIMTech in 2002—introduced a new framework to fully automate quality function deployment (QFD), a planning methodology for translating customer needs or the ‘voice of the customer’ into appropriate product features.

However, the voice of the customer often has multiple interpretations, especially when it comes to physical parameters like length or size. Accordingly, the manual evaluation of each scenario through QFD can be complex, time-consuming and error prone due to human fatigue.

© A*STAR Research

To address this ambiguity, then-GIMT Deputy Director Nai Choon Ho and Li Pheng Khoo from Nanyang Technological University, Singapore (NTU Singapore) applied possibility theory and fuzzy arithmetic in a 1996 publication to transform vague customer voices into data that can be used for unbiased decision making3.

In doing so, their approach enabled the identification of critical design characteristics to be improved in manufacturing systems. The following year, the Institute of Materials Research and Engineering (IMRE) was established. Diving straight into action, IMRE’s Swee Hin Teoh and colleagues fabricated a new flexible and biocompatible composite material—taking inspiration from how biological soft tissues are reinforced by collagen and elastic fibers.

As detailed in Advanced Composite Letters, the team fortified a composite material made of polyurethane elastomers with a knitted fabric of polyester fibers to improve its mechanical properties without sacrificing flexibility4.

With its unique properties, their material could have applications in everything from artificial organs to controlled drug delivery. 1997 ultimately proved to be an eventful year, with the onset of the Asian financial crisis. To ensure Singapore would remain competitive, the biomedical sciences was identified as a key growth pillar of the economy.

This pivot to biotechnology resulted in the reorganization of the NSTB in 2000 into the two councils that are still active today at A*STAR. NSTB’s physical sciences and engineering RIs would be housed under the Science and Engineering Research Council (SERC), which would in turn support manufacturing in the electronics, communications, chemical and general engineering sectors.

Meanwhile, the Biomedical Research Council (BMRC) was tasked to transform Singapore into a biomedical sciences powerhouse. By building a strong base in both basic and applied R&D, more multinational pharmaceutical and biotechnology companies would ideally converge in the country, just like the semiconductor companies decades before.

By January 5, 2002, NSTB was renamed the Agency for Science, Technology and Research (A*STAR). With SERC and BMRC in place, the RIs were finally brought together under an overarching body, encouraging collaboration and ensuring that Singapore’s R&D agenda was clearly delivered by a single agency.

Supercharging the biomedical sector

To further boost the country’s biomedical capabilities, multiple biomedical sciences RIs were set up to complement the IMCB and the Bioprocessing Technology Institute (BTI). Leading the way was the Genome Institute of Singapore (GIS) established in 2000, a national initiative that sought to use genomic sciences to improve public health. The Singapore Immunology Network (SigN) followed suit in 2005, and then the Singapore Institute for Clinical Sciences (SICS) in 2006.

In a pioneering Cell paper published in 20005, IMCB researchers showed that a gene aptly named Partner of Inscuteable (Pins) was required for the Inscuteable gene to function in coordinating and mediating asymmetric cell division in fruit flies. Though such a study may not seem immediately relevant to humans, the team’s findings could have crucial implications for neural disorders and neurodevelopment in humans.

“In neural stem cells, asymmetric cell division is a fundamental strategy for balancing self-renewal and differentiation,” explained Fengwei Yu, who was then a PhD student at IMCB. “Impaired asymmetric divisions could lead to the formation of brain tumors.”

Continuing what is now a tradition of excellence even from a young A*STAR, Brenner’s team at IMCB published a landmark Science paper in 20026, detailing the whole-genome shotgun assembly and analysis of the pufferfish Fugu rubripes, the second vertebrate genome to be mapped in detail (with the first being the human genome). It was also the first vertebrate genome to be sequenced using the whole-genome shotgun approach, which involves chopping the genome into millions of overlapping bits for sequencing.

“The main motivation for sequencing the pufferfish genome was to better understand the human genome,” explained lead author Byrappa Venkatesh, former Professor and Research Director at IMCB. At the time, it was known that the human genome contained around 3,000 Megabase pairs (Mbp) with repetitive sequences known as ‘junk’ DNA comprising over 50 percent of the genome.

“In contrast, the pufferfish genome was only 380 Mbp and less cluttered with junk, yet encoded a similar repertoire of genes to the human genome,” added Venkatesh. “By comparing the pufferfish and human genomes, we were able to identify about 1,000 human genes that were missed by other methods.”

Similarly, over at the GIS, a team led by Senior Group Leader Huck Hui Ng investigated gene regulation in mammalian embryonic stem (ES) cells, with their findings culminating in a 2008 article published in Cell7. In the realm of regenerative medicine, ES cells are of particular interest due to their pluripotency, or ability to give rise to cells of various lineages.

“Transcription factors and their control networks are central to the core of these properties,” noted Ng, who is today Assistant Chief Executive of the BMRC. “We need to have a solid understanding of ES cell and even induced pluripotent stem cell transcriptional regulatory networks to gain a full picture of the molecular controls underpinning stem cell differentiation and regeneration.”

The team’s study was the most comprehensive mapping of transcriptional regulatory networks in ES cells at the time. “It was also a technical breakthrough, given the datasets’ scale and the combined analysis of the multiple datasets,” Ng recalled. “For a number of years, it was the de facto reference guide for mapping pluripotency-related proteins that bound to DNA.”

Spotlighting the physical and engineering sciences

Along with BMRC reaching milestones in succession, SERC RIs continued to make gains in emerging areas like novel materials and magnetic skyrmions even throughout the 2010s.

In a 2016 study published in Nature Photonics, Qian Wang and Jinghua Teng—a Scientist III and Principal Scientist at IMRE, respectively—described a new way to harness light to reversibly adjust optical components. Along with collaborators from NTU Singapore and the University of Southampton in the UK, the two showed that applying ultrashort pulses of laser light to certain areas of an optical film could tweak its properties. Compared to conventionally bulky components, the optical devices the team produced through their method were much flatter and smaller—allowing them to be easily integrated into existing optical systems8.

Magnetic skyrmions also represent another exciting area of frontier technologies currently being explored by A*STAR scientists. In a breakthrough Nature Materials paper published in 2017, a team of DSI and IHPC researchers demonstrated an innovative technique for making ultrathin films that could host skyrmions with tunable properties9.

While they may sound like something straight out of a science fiction novel, skyrmions are in fact nanoscale spin structures formed in certain magnetic materials, and behave like mobile magnetic particles. However, for them to be considered for industrial applications, their properties must be modifiable under ambient conditions.

By varying the thickness of the individual layers within the multilayer film, the team managed to directly modulate various physical properties of skyrmions, including size, density and stability. “Our initial efforts focused on establishing and tailoring their room temperature properties,” noted first author Anjan Soumyanarayanan, currently a Senior Scientist at IMRE and Assistant Professor at the National University of Singapore (NUS). Since then, his team has realized their electrical manipulation—that is, the controlled ‘writing’ and motion of skyrmions within devices10,11.

Though it’s early days yet, their findings could lead to stable and highly scalable devices representing the next generation of edge computing technologies. Promisingly, these devices could also be easily integrated into microchips using manufacturing processes already used in the electronics industry.

The 2010s also witnessed the development of the first made-in-Singapore anti-cancer drug. Called ETC-159, the small-molecule drug candidate was jointly developed by the national drug discovery and development platform Experimental Drug Development Centre (EDDC), housed under A*STAR and Duke-NUS Medical School. ETC-159 inhibits aberrant Wnt signaling to target a range of cancers, including colorectal, ovarian and pancreatic cancers12. After entering clinical trials in June 2015, ETC-159 is now being assessed for both safety and efficacy as part of Phase 1B trials.

Reaping the rewards of translational research

Even when faced with a global pandemic caused by SARS-CoV-2, A*STAR continues its record of excellence. The agency’s researchers along with collaborators from Tan Tock Seng Hospital (TTSH) were among the first to jump into action once the virus landed on local shores.

Sustained by sheer willpower amid long, sleepless nights, the team managed to develop the Fortitude COVID-19 test kit within a matter of weeks—an unprecedented turnaround time given that diagnostic kits were only made available months into the previous 2003 SARS outbreak. Since the frenzied days of February 2020, the Fortitude kit has been deployed in over 45 countries globally.

Behind the scenes, A*STAR’s researchers also worked hard to decipher the coronavirus’ mysteries. For instance, during the pandemic’s first few months, the team of Lisa Ng—currently Executive Director of BMRC as well as A*STAR’s Infectious Diseases Labs (ID Labs)—investigated the genetics underlying the individual variations in clinical response13. Notably, the same team also identified a deletion of 382 nucleotides in the SARS-CoV-2 genome associated with a milder infection and better clinical outcomes14.

Meanwhile, in a recent Cell publication, a team led by SIgN’s Cheng-I Wang revealed that contrary to popular belief, certain neutralizing antibodies against SARS-CoV-2 could enhance viral fusion and even the formation of harmful multinucleated, giant cells called syncytia15.

With COVID-19 shining a spotlight on biomedicine, along with developments in genomics and data analytics, the 2020s have so far seen a blitz of biomedical data. However, integrating disparate datasets to gain actionable insights is easier said than done, especially when it comes to single-cell sequencing. After all, even minute experimental differences from various datasets can add up to create large variations called batch effects.

To overcome these inconsistencies, Wang’s SIgN colleague Jinmiao Chen sought to determine the best algorithmic method to correct batch effects in single-cell sequencing datasets16. Testing 14 algorithms, Chen and her team identified three algorithms most suited to integrating increasingly large biological datasets.

Beyond the laboratory, the pandemic has also disrupted supply chains worldwide, prompting factories to quickly pivot to more resilient manufacturing processes. Keeping the tradition of industry collaboration alive, I2R researchers led by Principal Scientist Xiaoli Li recently developed an intelligent framework to boost the prediction of remaining useful life for industrial machines17.

In a shining example of man-machine collaboration, the framework combines features derived from deep learning algorithms with handcrafted features manually inputted by data scientists. After applying their framework to evaluate a deteriorating aircraft engine, the team found that their approach outperformed current state-of-the-art artificial intelligence (AI) algorithms.

Such developments pave the way for manufacturing workflows that are less prone to external shocks. “People often say deep learning leads to the best results,” shared Li. “Our research demonstrates that human domain knowledge is equally valuable and critical in boosting system performance. By integrating AI and human intelligence, we can achieve the best explainable outcomes.”

As we move into a post-pandemic world, A*STAR remains committed to advancing knowledge and innovation across all domains.

In the realm of robotics, scientists from I2R have developed a lightweight mobile robot positioning system that works indoors. By using a cost-effective WiFi-based technology, the system can be readily applied in any environment that already has WiFi18.

On the other end of the spectrum, IMRE researchers along with NUS collaborators have also recently demonstrated in Science Advances a new approach for hyperspectral microscopy using off-the-shelf components, making the study of live cells more accessible19.

Making an impact on the public sector and industry

Through the examples thus far, A*STAR’s focus has clearly expanded from its early forays in biomedicine and manufacturing. Today, basic research that addresses grand challenges in science, known as use-inspired basic research (UIBR), forms a key part of the agency’s mission. But equally indispensable is the applied and translational research (ATR) that provides solutions to societal and industry needs.

Both UIBR and ATR helped Singapore face the threat of COVID-19 head-on and will certainly prove useful for future challenges, from rising drug resistance to the ongoing climate crisis. Already, A*STAR is making headway on these fronts. Some notable efforts include finding novel pathways to cripple tumor growth20 as well as redesigning catalysts to better generate clean energy21.

Ultimately, however, the pandemic highlighted what A*STAR had long known: the importance of building deep capabilities in science and technology to not just benefit the public sector and industry—but also Singaporeans and the world at large. This message was reinforced with the release of the latest five-year S&T roadmap, now called the Research, Innovation and Enterprise 2025 (RIE2025) plan.

The RIE2025 criss-crosses four strategic domains, namely human health and potential (HHP); Smart Nation and digital economy (SNDE); urban solutions and sustainability (USS); and manufacturing, trade and connectivity (MTC).

Considering that human capital is Singapore’s most valuable natural resource, A*STAR’s Singapore Institute for Clinical Sciences (SICS), KK Women’s and Children’s Hospital, National University Health System and NUS are on a mission to maximize human potential—embarking on the Republic’s largest and most comprehensive birth cohort study yet. Called Growing Up in Singapore Towards Healthy Outcomes (GUSTO), the collaboration tracks local mothers and their offspring from early pregnancy and as the children grow up.

“The GUSTO kids are now tweens (9 to 12 years old), so we will consider how this exciting rapid time of development is linked to earlier determinants and exposures,” explained Johan Eriksson, Executive Director at SICS. “As it is a period of increasing social exploration, aspects of mental wellness and social adjustments will be considered, alongside responses to the digital universe.”

“Over the next few years, Singapore will have a cohort of the most deeply phenotyped teenagers in the world,” added Yap Seng Chong, former Executive Director at SICS. “This will give us a wonderful opportunity to discover more about adolescent health, development and behaviors. Many of the findings will apply not only in Singapore, but in urban settings across Asia and beyond.”

Meanwhile, to help Singapore achieve its Smart Nation ambitions and propel the Republic towards a true digital economy, I2R is collaborating with the Land Transport Authority (LTA) to develop the next generation of intelligent traffic light control systems tailored to Singapore’s busy roads. Aptly called the CoopeRative and UnIfied Smart Traffic SystEm (CRUISE), the system integrates near real-time contextually rich datasets from frontier technologies like connected autonomous vehicles with AI to optimize traffic light and pedestrian crossing timings.

“It is envisioned that CRUISE will result in safer roads and cleaner air in Singapore by enhancing the responsiveness of emergency services and reducing traffic congestion,” commented Jaya Shankar, Division Head of Intelligent Transportation Systems at I2R.

Through the newly established Singapore Institute of Food and Biotechnology Innovation (SIFBI), A*STAR is developing R&D capabilities for agri-food tech solutions to support the nation’s ‘30 by 30’ goal. As Singapore imports over 90 percent of its food, the nation has set its sights on producing 30 percent of its nutritional needs locally by 2030.

SIFBI was inaugurated with the aspiration to provide end-to-end capabilities in the food innovation value chain for a more secure and sustainable food ecosystem. For instance, the Natural Product Library (NPL) housed at SIFBI represents one of the world’s largest collections of microbes, fungi and plant biospecimens and bioactive extracts. Screening campaigns are regularly undertaken with collaborators to identify natural bioactive compounds for industrial applications as well as natural preservatives and novel alternative protein ingredients to be used in food.

Finally, with manufacturing placing Singapore firmly on the global map three decades ago, the city-state is still making inroads in advancing the sector today through the A*STAR Model Factory Initiative.

Given that manufacturing forms around 20 percent of the country’s GDP, Singapore must embrace industrial digitalization—sometimes referred to as the 4th Industrial Revolution or Industry 4.0.

The A*STAR Model Factory Initiative was set up as part of the vision to transform the Republic into a technology innovation hub for manufacturing: a pilot location for cutting-edge technology and systems, a thought leader and a first mover in growth areas.

Through the Model Factory @ SIMTech, the Model Factory @ the Advanced Remanufacturing and Technology Centre (ARTC), and the Next Generation Hyper Personalisation Line (NHGPL) @ ARTC, the initiative aims to provide a platform for research performers, end users, technology providers and system integrators to jointly innovate, test and demonstrate advanced manufacturing technologies.

Even with three decades under its belt, A*STAR is still relentless in addressing science’s most fundamental questions while continuing its mission to improve lives through applied cross-disciplinary research.

In the years to come, the agency remains committed to further raising Singapore’s profile as a major player in the scientific landscape by engaging in more international R&D collaborations, but without losing sight of domestic needs. Given A*STAR’s adaptability and appreciation for society’s evolving demands, it has—and always will— embrace innovation. Happy 30th anniversary, A*STAR!

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This article was made for A*STAR Research by Wildtype Media Group