The perfect model organism could hold the key to effective liver cancer treatments. Old plastic bags and bottles could be transformed into new materials. Global collaboration could pave the way towards a unified understanding of the human genome. Advancements like these are bold, impactful and led by exceptional researchers.
To support Singapore’s research landscape and the scientists behind such significant projects, the National Research Foundation Singapore (NRF) launched two funding programmes: the NRF Investigatorship (NRFI) for leading researchers to conduct groundbreaking, high-risk research, and the NRF Fellowship (NRFF) for early-career scientists to carry out independent research over a five-year period.
The NRFF is extremely competitive and open to all areas of science and technology as well as all nationalities. After five years of research, fellows will be offered tenure-track faculty positions at partner research institutions in Singapore.
The class of 2023 includes an impressive 10 researchers from A*STAR and comprises four investigators and six fellows. In this issue of A*STAR Research, we take a look at their ongoing journeys to solve the region’s greatest problems and position Singapore as a global research leader.
NRF Investigatorship (NRFI)
For research leaders in pursuit of high-risk, groundbreaking work
JAY W. SHIN
Group Leader, Genome Institute of Singapore
Ribonucleic acid, or RNA, was discovered over six decades ago. But there has never been a more exciting time for RNA research than now, in an emerging era of advanced therapeutics and targeted vaccines.
Across the globe, researchers are making great strides in uncovering the potential applications of these tiny information-packed molecules. At the Genome Institute of Singapore (GIS), Jay W. Shin and his team work to read RNA sequences to reveal a cell’s ‘identity’.
By harnessing new technologies, Shin and his team decode the human genome and profile cellular traits—such as how each cell responds differently across thousands of drugs—to better understand health and disease. Their end goal is to make single-cell genomics more scalable, affordable and accessible to aid in the development of next-generation therapeutics.
Shin and his team actively participate in global efforts like the Human Cell Atlas, which aims to build a standardised reference map of the human body. Similar to the Periodic Table of Elements, the Human Cell Atlas will make results from labs like Shin’s more testable, interpretable and interoperable for researchers around the world.
“Genomic research is less like the Olympics and more like the United Nations. Engaging with global communities creates opportunities to represent your science and work collectively to tackle global health issues. Knowledge gained through the global community can also inspire new research and breakthroughs here in Singapore.”
Senior Principal Investigator, Infectious Diseases Labs
Marco Vignuzzi entered the field of infectious diseases in the ‘90s, when labs had just begun exploring vector-borne viruses, and their greatest concerns were the human immunodeficiency virus (HIV) and influenza. By the time of COVID-19, Vignuzzi had weathered waves of viruses like SARS, dengue, Zika and chikungunya—building decades’ worth of research in pandemic preparedness, prediction and prevention.
Today, Vignuzzi and his team at the A*STAR Infectious Diseases Labs (ID Labs) work to uncover how these viruses emerge and adapt to new host species in preparation for the next worldwide viral threat.
Vignuzzi is no stranger to global partnerships; he considers them crucial for managing worst-case scenarios. At the height of the COVID-19 lockdowns, Vignuzzi helped bring together research institutes across over 30 countries in the Pasteur Network.
His lab was also a part of the University of California San Francisco’s Quantitative Biosciences Institute Coronavirus Research Group, the first to begin reviewing existing compounds which could impact human proteins related to COVID-19 infection—quickly discovering 69 agents.
Vignuzzi hopes to involve more researchers from Singapore in such collaborations. He highlights the country’s unique position, which allows it to pilot new policies and research from global networks for the benefit of the Southeast Asian region.
“I want to create a legacy of young researchers trained in my lab to tackle the big questions relating to RNA viruses. I admire the Singaporean dream, that everyone has a role to play and that the whole population can rise by using each other’s talents intelligently, strategically and for the common good.”
WAI LEONG TAM
Associate Director and Group Leader, Genome Institute of Singapore
One in three Singaporeans is likely to develop cancer in their lifetime. To reduce the economic, social and health impacts of this prevalent disease, Wai Leong Tam and his team at the Genome Institute of Singapore (GIS) look to understand and combat cancer from a metabolic standpoint.
Rather than focusing on eliminating cancer cells, the team takes a unique approach: their work explores the tumour microenvironment and the diverse cell types within it, such as fibroblasts and immune cells.
One key finding from Tam and colleagues was that tumour microenvironment cells supply nutrients to fuel cancer cell growth in a process called metabolic crosstalk. The team believes that intercepting the flow of these nutrients is key to eliminating tumours and combatting cancer.
By adopting a patient-centric approach and collaborating with leading oncologists at institutes like the National Cancer Centre Singapore and the National University Cancer Institute, Singapore, Tam works towards identifying new targets within the tumour microenvironment that can be fed into drug development programmes.
“The most important attribute for cancer researchers is a commitment to doing good for society. We must have the conviction that our findings matter in order to see our research to fruition. There is no greater satisfaction than seeing how your discoveries can make a positive impact in the quality of life for cancer patients.”
Associate Director, Genome Institute of Singapore
Roughly 15 years ago, Yue Wan, a bright-eyed graduate student looking to work with RNA, joined Howard Chang’s lab in Stanford University. At the time, researchers would have to study RNA structures one at a time to understand their function—a task considered worth doing, as very little was then known about long non-coding RNA.
Not long after, high-throughput or next-generation sequencing technologies became available, allowing the team to develop a new method to study RNA. By capturing single- and double-stranded bases along an RNA molecule and combining that with deep sequencing, the team could obtain static pictures and structural dynamics of the yeast transcriptome.
Since then, Wan has started her own research group at the Genome Institute of Singapore (GIS) and built an international group of collaborators. The field of RNA structurenomics continues to grow. Wan and collaborators have developed new strategies to map RNA-RNA and RNA-small molecule interactions, as well as detect RNA sensors.
More recently, they have begun exploring single cells and single molecules to identify potentially diverse RNA structures within each cell. By understanding these structures, scientists can then design new small molecules to inhibit them, expanding RNA’s role as a potential drug target.
“RNA has dramatically changed the global therapeutics landscape. RNA as vaccines is just the tip of the iceberg for using RNA in medicine—advances in new modalities and delivery strategies will greatly accelerate the ability to use RNA as a therapeutic.”
NRF Fellowship (NRFF)
For early career scientists in pursuit of independent research
Junior Investigator, Institute of Molecular and Cell Biology
The human body is large and complex, comprising roughly 37.2 trillion cells. Zebrafish, on the other hand, are far smaller subjects that share more than 70 percent genomic similarity with humans, making them ideal animal models to study disease mechanism and progression.
Chuan Yan was fascinated by zebrafish from his time at the National University of Singapore, first working as an intern and later pursuing a PhD degree in Zhiyuan Gong’s lab. As a graduate student, Yan created zebrafish models with liver cancer, which showed a disease pathology similar to humans.
Today, at the Institute of Molecular and Cell Biology (IMCB), Yan’s research continues to revolve around liver cancer—specifically therapy resistance in its management. In addition to being prevalent in Asia, where 70 percent of all new cases are diagnosed, liver cancer is also usually diagnosed at later stages, leading to a high mortality rate.
To tackle the scourge of liver cancer, Yan’s lab looks to better understand resistance to existing cancer treatments through single-cell transcriptomic sequencing as well as by developing ‘humanised’ zebrafish models to screen novel drug candidates.
“My goal as a scientist is to leverage single-cell sequencing and preclinical animal modelling to provide rapid translational solutions for a vulnerable population of therapy-resistant patients.”
Principal Investigator, Institute of Materials Research and Engineering
When Di Zhu first studied fibre-optic communications as an undergraduate student, light was mostly treated as waves, and information was encoded by turning it on or off. As he continued his research towards the field of quantum optics, such perceptions changed drastically, where light can be engineered into states of individual particles (what is called ‘single photon’) and carry information in superpositions of 0 and 1—serving as fundamental resources for quantum computing.
Zhu worked to make exceptionally sensitive detectors that could detect individual particles of light. He also made devices to create and manipulate quantum states of light.
Now at the Institute of Materials Research and Engineering (IMRE), Zhu aims to build photonic integrated chips that can process quantum information —a task that is hard to implement based on existing silicon-based platforms.
Turning to an emerging photonic material called thin-film lithium niobate, Zhu integrated it with superconducting nanowires to make a program circuit that can generate, control and detect single photons.
Over the next few years, Zhu hopes to acquire the necessary resources to establish his lab’s capabilities in fabricating these photonic chips. He also intends to work with local academic and industry partners to scale up the team’s technology.
“I always joke that my research is both cool and hot. Superconducting devices are really cold—around -270 degrees Celsius. Optical photons are really energetic—they have an ‘effective temperature’ of thousands of degrees Celsius. Integrating them is an aggressive combination.”
Emerging Group Leader and Deputy Head of Department,
Institute of Materials Research and Engineering
One man’s trash can be another man’s treasure. In Jason Lim’s research, one man’s discarded plastic can be a treasure for everyone—that is, once it is turned into essential compounds that contribute to a more sustainable economy.
Complementing his current work on developing functional materials from waste plastics, Lim believes that finding new ways to turn those plastics into useful small-molecule chemicals could also be a promising approach in plastics upcycling.
With the support of the NRFF, he aims to sustainably transform waste polyethylenes (PEs) into oxygenated compounds like organic acids, which are used extensively in many different industries with massive global demand. Mostly used for packaging materials like plastic bags, films and detergent bottles, PEs comprise the largest class of waste plastics produced today. They are often thrown away directly after use, making their life cycle particularly unsustainable.
Over the next few years, Lim hopes to develop innovative methods and solutions for transforming waste plastics into new materials and industrially-relevant commodity chemicals for a variety of applications. By improving our understanding of the fundamental chemistry behind these upcycling processes, he hopes to develop the next generation of energy and resource-efficient methods for large-scale plastic valorisation.
“I aim to inspire other young scientists to think big and develop bold solutions based on their areas of expertise to address some of society’s most pressing problems.”
JUN SIONG LOW
Almost like a game of cat and mouse, with each coronavirus strain that healthcare professionals manage to address, a new one seems to pop up not long after. Beyond SARS-CoV-2, the cause of COVID-19, there are many other coronaviruses in global circulation. Some of these cause the common cold, and some underwent zoonotic transmissions that led to epidemics such as SARS-CoV in 2003 and MERS-CoV in 2012.
Predicting what coronaviral threat might come next is a gargantuan task because of the sheer number of them that exist in the animal kingdom and their genetic diversity. Rather than to try to pinpoint the next pandemic-causing virus, Jun Siong Low and his team at the Institute for Research in Biomedicine and ETH Zürich believe that a promising strategy is to identify a common ‘Achilles heel’ among all coronaviruses.
So far, Low and his colleagues have isolated antibodies that can neutralise all variants of SARS-CoV-2, SARSCoV, MERS-CoV and common cold coronaviruses. These antibodies target the conserved fusion peptide region of the viruses’ spike protein, thus identifying the fusion peptide as a potential target for the design of a universal coronavirus vaccine. Currently a postdoctoral fellow at ETH Zürich, Low will return to A*STAR in 2024 to study how to exploit our immune cells to tackle infectious diseases and cancers.
“My lab aims to better understand our immune system so we can exploit it for therapeutic purposes. Over the longer term, my goal is to contribute to the scientific community in Singapore, educate the younger generation about immunology, and pass on the thrill of scientific research.”
Emerging Group Leader and Deputy Department Head,
Institute of Materials Research and Engineering
While light-emitting materials may seem abstract, they are used in a wide range of everyday applications like displays and sensors. A clear understanding of organic luminescent materials could light the way towards more sustainable energy-efficient technology for various industries and individual consumers.
This is the dream of Le Yang, an emerging Group Leader at the Institute of Materials Research and Engineering (IMRE), leading the Printed Organic Flexible Electronics and Sensors (PROFESS) Group. She leverages her passion for optoelectronics and energy-efficient electronics to better understand and apply the spin-dependent behaviour in organic luminescent materials.
With a better understanding of the photophysical and electrochemical processes behind these materials, the team hopes to develop non-electronic, optoelectronic and electrochemical display and sensing technologies, which may find novel use cases in sustainable efforts such as urban smart farming and energy-efficient devices.
Beyond the NRFF, Yang and her team are also working on advancing non-invasive, real-time wearable solutions for on-skin metabolite biosensing, useful in digital healthcare and even forensics.
“The Singapore NRF Fellowship empowers me to explore challenging ideas, synergistically with the local and global community. I hope to grow with the ecosystem and establish myself in the field of organic luminescent materials and devices.”
Principal Investigator, Institute for Infocomm Research
Unlike the fictional stories presented in popular media like The Terminator and Black Mirror, NRF Fellow Mengmi Zhang believes that when robots are capable of performing human tasks, they will benefit society by doing what humans do not want to.
In her work, Zhang aims to close the gap between biological and artificial intelligence (AI). One aspect of AI that Zhang hopes to improve is visual search—a common daily activity for people, but particularly difficult for AI to do because of a lack of prior contextual knowledge and memory guidance. To enhance visual search quality, Zhang marries neuroscience and AI by exploring high-level cognitive functions in the brain and applying them to AI.
With the support of the NRF Fellowship, Zhang aims to further her interdisciplinary research into new AI technologies that can be deployed in various applications. Ultimately, such technologies could take over risky tasks that endanger human lives, detect neurological conditions in clinical care, and potentially augment human intelligence with AI-assistive hybrid biochip implants.
“It takes a village to carry out great science, which is why I plan to keep expanding my professional networks. With the combined efforts of scientists all over the world, my long-term research goal is to equip AI with the cognitive abilities to address tasks that are fundamental to human intelligence.”