Key Programme-level Projects

National Research Foundation (NRF) - Competitive Research Programme

Research funding is one of the key indicators of research performance. Belowis an NRF CRP won by our faculty members.

Our CoS team:
 
Lead PI: Prof. Dr. Gerhard Grüber (SBS)
Co-PIs: A/Prof. Roderick Bates (SPMS); A/Prof. Kevin Pethe (SBS/LKC)
 
Other team members:
 
Co-PIs: Prof. Alex Matter (Experimental Therapeutics Centre and D3, A*STAR), A/Prof. Thomas Dick (Yong Loo Lin School of Medicine, NUS)

Microbes have developed into specialized organisms, inhabiting nearly every ecosystem on today’s earth. This requires elaborate adaptation mechanisms to survive and thrive in these ecosystems. Adaptation of pathogenic bacteria such as Mycobacterium tuberculosis (Mtb) to its human host is possible due to their fascinating repertoire of genetic and biochemical mechanisms that allow them to adapt to their environments. During evolution Mtb employed a unique protein orchestra to synthesize the energy currency ATP (Adenosine triphosphate) in the pathway of oxidative phosphorylation, enabling the pathogen to survive in oxidative, and hypoxic environments inside granulomas. This energy producing pathway represents potential drug targets.
 
New antibiotics to fight drug resistant Tuberculosis bacteria are urgently needed. To develop new medicines against these superbugs we need to understand how the molecular machines that make up the tubercle bacillus work. We unraveled new mechanisms inside the critical energy generating machines, called cyt-bd oxidase and F-ATP synthase, identified (i) novel drug epitopes of these machines, (ii) novel compounds blocking energy generation and (iii) a novel epitope of the existing TB-drug bedaquiline. Our discoveries represent the missing step for the development of a rational sterilizing drug combination targeting oxidative phosphorylation for multi-drug and extensively drug resistant tuberculosis.
 
 
Figure 1: Oxidative phosphorylation pathway in Mtb, and molecular targets for drug combination targeting the cyt-bd and F-ATP synthase.

 

Ministry of Education (MOE) - Academic Research Fund (ACRF) Tier 3 Programme

Research funding is one of the key indicators of research performance. MOE AcRF is... Below are several active MOE AcRF Tier 3 Programmes won by our faculty members since 2011.

Our CoS team:

Lead PI: Prof James P Tam (SBS)

Co-PIs: Assoc Prof Julien Lescar (SBS), Assoc Prof Liu Chuan Fa (SBS); Assoc Prof Sze Siu Kwan (SBS)

Our program focuses on a new family of enzymes known as peptide ligases and the rules to design ligases from proteases. The knowledge gained will provide fundamental insights to engineer novel synthetic ligases as catalytic “molecular staplers” for bonding chemicals, proteins, polymers and inorganic materials with unique site-specificity and exquisite efficiency. In turn, these advances will influence research and development of biochemical, medical, pharmaceutical, food and material sciences.

Enzymes, which catalyze >5,000 types of reactions, are bio-transformers and engines of life. They are also enabling tools for research and useful commodities for industrial applications. Proteases, enzymes which break peptide bonds, are ubiquitous, with >400,000 found in databases and >4200 characterized. In contrast, peptide or protein ligases, peptide-bond-forming enzymes, which catalyze the reverse reactions of proteases are poorly characterized (Figure 1). Many are ATP-dependent and exist as protein complexes. Consequently, they are not applicable for biochemical uses in cell-free systems. Stand-alone and “ATP-independent” peptide ligases are the enzymes that would be highly useful for in-vitro biochemical reactions, but they are exceedingly rare. Thus far, only a few such ligases have been characterized. Hence, the discovery and the ability to engineer “ATP-independent peptide ligases” offer many exciting new possibilities and an open-ended research program to explore new frontiers in science and engineering.


Our CoS team:

Lead PI: Prof Nikolay Zheludev (SPMS)
Co-PIs: Prof Shen Zexiang (SPMS); Assoc Prof Cesare Soci (SPMS); Assoc Prof Zhang Baile (SPMS); Asst Prof Chong Yidong (SPMS); Asst Prof Gao Weibo (SPMS); Asst Prof Ranjan Singh (SPMS)

The project aims to develop ground-breaking enabling photonic technologies, new photonic devices and functional materials underpinned by new ideas in Quantum and Topological Nanophotonics that are among the most promising emerging directions of fundamental research.

Quantum nanophotonics arises on the border between deep quantum physics of light and nanotechnology, and focuses on the study of interaction of photons with matter at the nanoscale. It aims at radically new ways to control, generate, compute, communicate, and measure with quantum states of light and matter for applications in information processing, memories, imaging and sensor devices, and for designing new functional quantum materials. Topological nanophotonics is on the crossroads between the science of light and the mathematics describing properties under continuous deformations. Topology is another powerful design degree of freedom, which opens a path to fundamentally new states of light and matter, novel photonic circuitry, laser and optical components tolerant to imperfections, and new functional materials.

In the project the NTU team will collaborate with a cohort of world-class researchers from ETH Zurich, Stanford and Cornell, as well as with reserchers in the A*STAR, NUS and SUTD.

Our CoS team:

Lead PI: Prof Stephan Schuster (SBS)
Project PIs: Prof Stephen Schuster (SBS/SCELSE); Prof Yehuda Cohen (SBS/SCELSE); Assoc Prof Federico Lauro (ASE/SCELSE)
Co-PIs: Prof Staffan Kjelleberg (SBS/SCELSE); Asst Prof Mikinori Kuwata (ASE); Asst Prof Liang Yang (SBS); Prof Peter Steinberg (UNSW/SBS)

Other team members:

Co-PIs: Prof Peter Little (NUS/SCELSE); Asst Prof Victor Chang (CEE/SinBerBEST); Dr Ng Lee-Ching (NEA)
 

The air we breathe contains millions of microbes, yet we are largely unaware of what they are, what they do and how they respond to changing environmental conditions. Air is a key route of global microorganism cycling and a major source of human microbial exposure, but it remains the last of the Earth’s major ecosystems (after terrestrian and aquatic) to be explored for microbial life.

Each cubic meter of air contains thousands to millions of diverse microorganisms – fungi, bacteria, archaea, and viruses – aerosolised from humans and a variety of environmental sources, and influenced by factors including particle size, airflow, irradiation and humidity. Indoors, air is filtered and recirculated, and occupants and surfaces can act as sources and sinks, accumulating and resuspending settled or filtered biological and particulate matter. Evidence is emerging that airborne microorganisms in indoor spaces can differ substantially from outdoor communities, with less diversity and higher bacterial loads. However, the extent and impact of such changes on indoor and airborne microbial communities are not understood, particularly in the tropics.

SCELSE’s Air Microbiome integrated programme focuses on Singapore’s urbanised tropical environment. Modern tropical locations are unique because they offer a range of natural and artificial climatic conditions, to which the microbes respond. Central ventilation and cooling systems may quickly bring relief to the hot ambient temperatures and high humidity, but this action may result in changes to the air microbial composition, function and activity. Increasing numbers of people are spending more and more time indoors, immersed in surrounding microbial conditions that have yet to be discerned. Exercising control over the conditions of circulating air such as pressure and humidity may provide a means to reduce or eliminate potential health risks.

Technological advancements are only now enabling the effective extraction of biological information from the air in the form of DNA and RNA. Deriving knowledge from such samples requires an approach that encompasses not only genomics, but also microbial ecology, chemistry and physics. The Air Microbiome programme adopts such a multidisciplinary approach in its pioneering exploration of the sources, function and ecology of urban air microbiomes in this little-explored ecosystem. The research employs sampling designs informed by aerosol physics and theoretical frameworks based on ecology, adaptive responses and systems biology. Experimental aerosol systems explore microbial interactions and behaviours that are unique to the air microbiome. 

Specific research themes for this programme include:
  • Environmental genomics – investigating the diverse microbiological communities of unknown composition and function harboured by air;
  • Ecological connectivity – describing the dynamic network of sources and sinks that exists in the urban air ecosystem;
  • Adaptive responses – understanding how physicochemical parameters induce molecular responses in airborne microbiota.

Our CoS team:

Lead PI: Prof Daniela Rhodes (SBS)
Co-PIs: Prof Lars Nordenskiöld (SBS); Prof Phan Anh Tuan (SPMS); Assoc Prof Peter Droge (SBS); Assoc Prof Curt Davey (SBS); Asst Prof Sara Sandin (SBS)

Other team members:

Co-PIs: Prof G.V. Shivashankar (NUS); Prof Yan Jie (NUS)

In this project, we aim to conduct groundbreaking telomere biology research on how human cells prevent aging and become immortal. Since cancer cells are also able to enjoy eternal life, understanding these processes will ultimately pave the way to find cures for cancer.

Our program focuses on the regulation of chromatin structure at mammalian telomeres. Whilst functional studies have identified multiple mechanisms that critically impact telomere function and how telomere defects lead to genome instability, key information on the unique underlying structural and dynamic properties of telomere chromatin is lacking. Our central aim is to provide an understanding at the molecular level of the multiple mechanisms that regulate telomere chromatin structure, dynamics and stability, thus leading to novel insights into the biology of telomeres. Our ultimate aim is to apply this knowledge to address telomere malfunctioning in human aging and cancer.

Our CoS team:

Lead PI: Prof Nikolay Zheludev (SPMS)
Co-PIs: Prof Shen Zexiang (SPMS); Assoc Prof Cesare Soci (SPMS); Assoc Prof Wang Qijie (SPMS); Assoc Prof Sun Handong (SPMS); Assoc Prof Fan Hongjin (SPMS)

Other team members: Prof Shum Ping (EEE) '

Objective of the programme is to generate a knowledge base for new photonic technologies with 10+ year outlook.

The DPT Programme develops radically new nanotechnology-enabled artificial dynamic and reconfigurable photonic materials and components as a novel elemental base of revolutionary free-space, fibre and planar waveguide devices and optical nanocircuits, thus providing ground-breaking solutions for telecoms, energy, light generation, imaging, lithography, data storage, sensing, medicine, security and defence applications. By advancing the physics of control, guiding and amplification of light in nanostructures and by developing new nanofabrication techniques and methods of growth, hybridisation and integration into the waveguide and fiber environment of different novel material structures, the programme aims at developing disruptive technological solutions allowing for ultra-high-density integration, the lowest possible energy levels and the highest speeds of optical switching and data processing.

Three deeply interlinked research strands aim to generate a knowledge base for new technologies with 10+ year outlook: reconfigurable, dynamic and quantum metamaterials; reconfigurable micro/nano-fibers and cognitive photonic systems; nanolasers, spasers and nano-meta-materials for electromagnetic technologies.

The DPT Programme resulted in the formation of the Centre for Disruptive Photonic Technologies (CDPT), which has had a major impact on the landscape of photonics research in Singapore. CDTP is now clearly a leading nanophotonics Centre in Asia and the main centre of Nanophotonics and Metamaterial research in the Country complementing a more applied research agenda of A*STAR institutions DSI and IMRE and it is also emerging as a major player internationally.