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The changemakers reimagining research in Singapore.

© A*STAR Research

Shaping a legacy of scientific excellence

15 Dec 2021

Honored with the President’s Science and Technology Awards, A*STAR researchers are shaping Singapore’s scientific landscape. Here, we spotlight three researchers who have pushed the boundaries in foundational biomedical research, translational engineering efforts and cross-cutting collaborations.

In 1675, Isaac Newton captured the essence of scientific progress when he said, “If I have seen further, it is by standing on the shoulders of giants.” Centuries since his famous statement, our collective scientific knowledge has grown in different ways, with certain fields gradually building up knowledge over time and others racing forward with incredible breakthroughs.

A*STAR understands that regardless of pace, extensive foundational work and collaboration remain the bedrock of scientific achievement. Hence, the agency’s research and development (R&D) efforts have always been to bridge decades of basic and applied sciences to meet strategic needs in sectors like healthcare and sustainability.

Through the years, many visionaries have led such endeavors to solve pressing issues, with their efforts recognized by accolades including the President’s Science and Technology Awards (PSTA), formerly known as the National Science and Technology Awards (NSTA). These distinctions are the highest national honors for scientists and engineers in Singapore, celebrating their seminal contributions in shaping the country’s R&D landscape.

As the agency commemorates its 30 years of R&D, we revisit efforts by A*STAR’s PSTA laureates. They have stood on the shoulders of giants while carving avenues for future impact-driven research spanning multiple disciplines— raising the bar for excellence at A*STAR and beyond.

Decoding the genetic story of Asian cancers

In the realm of health, shedding light on previously overlooked aspects of cancer are researchers like Patrick Tan, who has had a long-standing interest in the genetics of cancers endemic to Asia and other Asian-specific disease conditions. More recently in 2019, Tan took up the mantle of Executive Director at A*STAR’s Genome Institute of Singapore (GIS).

In collaboration with Bin Tean Teh from the National Cancer Centre Singapore and Steven Rozen from DukeNUS Medical School, Tan received the President’s Science Award in 2015 for unraveling the molecular underpinnings of Asian cancers, yielding insights into the environmental and clinical factors contributing to cancers distinct from those prevalent in the West. The national honor also helped elevate cancer research in Asia to global consciousness, as they later became the first-ever group from the region to win the prestigious American Association for Cancer Research (AACR) Team Science Award.

“We were struck by the observation that, throughout Asia, there were many areas where specific cancers occur at a very high incidence,” Tan said. As Asian ethnicities comprise a significant portion of the global population, their work revealed that certain cancers were not at all rare, and yet lacked attention from the scientific community.

For example, about 0.3 to 6 new cases of biliary tract cancer are recorded per 100,000 inhabitants globally. However, the incidence rate could be up to 96 per 100,000 males in the Thailand’s northeastern area. As Tan and team probed into this understudied cancer, they discovered critical alterations in the RNF43 gene1 , which was later found to be frequently mutated in colorectal tumors—the third most common cancer worldwide.

By identifying the mutations driving these tumors, scientists can develop novel approaches for early diagnosis and personalized therapies. “Improving outcomes for cancer patients will require managing patients with subtype-specific therapies, tailored to the molecular vulnerabilities of each subtype,” Tan said.

Besides showing how to distinguish high-risk populations2, Tan and colleagues’ pioneering work on gastric cancer has led to clinical trials for new interventions against this serious condition. Supported by the Singapore Translational Cancer Consortium, a new nationwide study is validating whether certain epigenetic markers can predict how well a patient responds to immunotherapies.

To usher in an era of disease prevention, the institute is also supporting the National Precision Medicine program, creating a database of 100,000 Singaporean genomes3 to uncover the molecular markers of diseases. Through these collaborative endeavors, Tan envisions A*STAR extending its legacy in delivering societal impact, contributing to the continued advancement of human health and well-being.

“Our motto at GIS is that ‘We read, reveal and (w)rite DNA for a better Singapore and world,’” he shared. “As the custodian of Singapore’s genomic data, the GIS database of genomic sequences will represent a game-changing platform that will power Singapore’s researchers for many years to come.”

Building liveable cities

Zooming out from the intricacies of our genetic code, researchers from A*STAR’s Institute of High Performance Computing (IHPC), Institute for Infocomm Research (I2R) and Singapore’s Housing and Development Board (HDB) have co-created another equally groundbreaking platform: a smart urban planning tool that garnered the President’s Technology Award in 2019.

Dubbed the Integrated Environmental Modeler (IEM)4, the platform combines computer models, sensors and localized climate data to simulate an area’s environmental conditions to facilitate building urban structures sustainably.

From residential to commercial developments, urbanization often comes at great cost to the planet— clearing out greenery, using carbon-heavy resources like steel and putting a strain on the electrical power supply.

With the effects of the climate crisis becoming more apparent than ever, the IEM team saw physics-driven modeling as the answer to sustainable urban development—helping city planners optimize structural designs for maximum comfort at minimal resource cost.

“Advanced modeling is important for urban sustainability as we can now conduct virtual trials before spending a large number of resources,” explained Wee Shing Koh, a Senior Scientist at IHPC. “For example, if the layout tends to trap heat, it will be undesirable to live in or costly to remedy over the building’s lifespan.”

Many materials used in urban environments, such as cemented pavements, tend to absorb solar energy as heat, whereas some buildings and vegetation provide shading and cooling effects. By simulating solar irradiance and shading, the IEM tool predicts how heat would impact wind flow. While wind and heated surfaces affect air temperature distribution, factors such as airflow and temperature in turn direct how audible noise propagates through an area.

To measure all these parameters, over 100 sensors were deployed across the country, highlighted Fachmin Folianto, a Principal Research Engineer at I2R. “All the sensors were powered by solar energy and they transmitted real-time data wirelessly,” he added.

Thanks to this integrated tool, users can readily visualize how different structures alter environmental conditions, leading to sustainably designed cities that leverage natural ventilation and lighting. Having scaled up IEM to cover island-wide airflow and solar irradiance, IHPC Senior Scientist Hee Joo Poh shared that new urban spaces can be designed to minimize their impact on existing neighboring residential estates.

Putting their platform into practice alongside HDB, the team deployed the IEM tool to design Singapore’s first smart and sustainable town, Tengah Town, analyzing wind channels and optimizing building layouts to promote natural ventilation.

“Winning the award gives us extra motivation and encouragement to push technological frontiers in urban environmental modeling,” Poh expressed. He is now leading the expansion of IEM’s features, which are set to simulate factors like aircraft noise, wind-driven rain and global climate change effects.

Given the modeling and simulation capabilities A*STAR has developed over the past three decades, Koh foresees that new and improved technologies will readily meet the needs on the ground. The team envisions that these smart planning tools will enable researchers and policymakers to formulate better plans to mitigate the effects of climate change, paving the way for more sustainable, comfortable and resilient cities.

Illuminating the future of bioprobes

As researchers dive into the inner workings of cells, science’s interdisciplinary nature is also in full display. After all, fluorescent dyes crafted by chemists and chemical engineers have become essential tools for visualizing the tiny yet complex cellular world. By tagging target molecules with color-emitting dyes to yield bioprobes, biomedical scientists can then monitor internal processes like cell death and detect compounds such as infection-fighting antibodies.

Conventional dyes, however, work best alone. While the molecules appear bright in dilute solutions, their emissions sharply diminish upon aggregation. But certain organic molecules behave otherwise. In a phenomenon aptly called aggregation-induced emission (AIE), packing these molecules together intensifies their fluorescent properties.

By figuring out how to control these light emissions, A*STAR Institute of Materials Research and Engineering (IMRE) Adjunct Investigator Bin Liu and collaborators discovered that AIE nanoparticles could be made 10 to 40 times brighter than the commercial quantum dots used for biomedical imaging5.

These unique fluorescent properties make for non-toxic reagents that not only produce high-contrast imagery but also enable real-time cell monitoring over longer periods. To find biomedical applications for their AIE nanoparticle technology, Liu and colleagues founded Luminicell, a spinoff company of the National University of Singapore.

By altering the nanoparticles’ size and surface properties, Liu and the team adapted the AIE materials to serve several use cases in research and clinical practice. For instance, to label specific cell components like protein biomarkers for disease, one might add to the nanoparticle surface molecules that bind strongly to the target. Meanwhile, to trace cell types like immune cells and cancer cells, molecules with excellent cell-infiltrating capabilities can be attached to the nanoparticles.

For her efforts in transforming fluorescence imaging6 with AIE molecules, Liu was honored with the President’s Technology Award in 2016. “The immediate impact was the enhanced visibility of our AIE nanoparticle technology,” she said, adding that the award catalyzed support for further development of AIE-powered solutions.

Since then, AIE has been shown to have applications in everything from cell tracing to light-based medical treatments. With their capacity to visualize the cellular world in greater detail, these nanoparticles could help guide cancer therapies and surgeries7.

“These applications have been achieved through precise molecular engineering to yield multifunctional AIE molecules, and from the thorough study of AIE particles’ photophysical processes,” Liu said.

For Liu, these significant strides in AIE-based bioprobes were made possible by collaborating with diverse sectors, enabled by the extensive network between A*STAR, universities and industry partners. Amid the agency’s interdisciplinary environment, her work exemplifies how spheres of expertise can overlap to create exciting new solutions, harnessing materials science for healthcare applications.

“A*STAR has nurtured many R&D talents and bridged the gap between fundamental science and translational research,” Liu said. “I hope that synergy among A*STAR and local universities could be achieved to build a stronger, safer and more sustainable society.”

By creating new knowledge and forging strong collaborations across Singapore’s scientific ecosystem, these PSTA awardees will continue to be strong ambassadors for A*STAR within Singapore and beyond.

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References

1. Ong, C.K., Subimerb, C., Pairojkul, C., Wongkham, S., Cutcutache, I., et al. Exome sequencing of liver fluke-associated cholangiocarcinoma. Nature Genetics 44, 690-693 (2012) | article
2. Huang, K.K., Ramnarayanan, K., Zhu, F., Srivastava, S., Xu, C. Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer. Cancer Cell 33, 137-150 (2018) | article
3. Wu, D., Dou, J., Chai, X., Bellis, C., Wilm, A., et al. Large-scale whole genome sequencing of three diverse Asian populations in Singapore. Cell 179, 736-749 (2019) | article
4. Poh, H.J., Koh, W.S., Liu, E., Zhao, W., Tan, S.T., et al. Modeling of urban heat island and noise propagation in Singapore. 4th International Conference on Countermeasures to Urban Heat Island, National University of Singapore (2016)
5. Li, K., Qin, W., Ding, D., Tomczak, N., Geng, J., et al. Photostable fluorescent organic dots with aggregation-induced emission (AIE dots) for noninvasive long-term cell tracing. Scientific Reports 3, 1150 (2013) | article
6. Qin, W., Ding, D., Liu, J., Yuan, W.Z., Hu, Y., et al. Biocompatible nanoparticles with aggregation-induced emission characteristics as far-red/near-infrared fluorescent bioprobes for in vitro and in vivo imaging applications. Advanced Functional Materials 22, 771-779 (2012) | article
7. Wu, W., Mao, D., Xu, S., Ji, S., Hu, F., et al. High performance photosensitizers with aggregation-induced emission for image-guided photodynamic anticancer therapy. Materials Horizons 4, 1110-1114 (2017) | article

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