Biosensors and Bioelectronics
- Assistive Technology/ Rehabilitation Engineering
- Atom Optics/ Ultracold Matter
- Biomedical Engineering & Devices
- Biometrics, Biophysics Optics
- Biosensors and Bioanalytics
- Cancer Biology
- Breast cancer
- Anti-tumour activity of enediyne natural products
- Chiral & Pharmaceutical Engineering
- Computational Biology
- DNA Packaging
- Gene Delivery
- Molecular Dynamics
- Mathematical Modeling
- Wiskott Aldrich Syndrome
- Spindle Assembly in Mitosis
- Cell Morphology and Migration
- Development and Disease
- Zebra Fish Development
- Wound Healing
- Alzheimer's Disease
- Genomics and Epigenetics
- Genetic Imprinting
- Computational and Functional Genomics
- Malaria Genomics
- Host-pathogen interactions
- Malaria Biology and Immunity
- Genetic Regulation of Biofilms
- Innate and Adaptive Immunity
- Integrin Adhesion Molecule and Complement Proteins
- Dendritic Cells
- Integrin Mediated Cell Adhesion and Migration
- Signaling in Inflammation
Ion Channels and Transport |
- Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
- Calcium Transport
- Natriuretic Peptides
- Peptide Synthesis Technology
- Peptide Vaccine
- Peptide Therapeutics
- Peptide and Protein Chemistry
- Disease Diagnostics
- Protein Structure and Function
- Disease Diagnosis
Soft Condensed Matter
Stem Cell Research:
- Human Embryonic Stem Cells
- Haematopoietic Stem Cells
- Thymocyte Development
- Designer Drugs
- Structure of Nucleosome Core Particles
- Micrographic Imaging
- Structure of Viral and Other Proteins
- Nuclear Magnetic Resonance
- Usage and Technology Development
- Transmembrane Helix-Helix Interactions
- Protein Structure and Function
- X-ray Crystallography
- Virus Host Interactions
- RNA Viruses
- Viral Host Cell Fusion
This is a multidisciplinary field in which fundamental sciences and emerging technologies integrate for,the 1) development of sensing devices to probe biological and physiological processes by applying state-of-the-art nanotechnologies and microfabrication technologies, as well as advanced electronic, electrochemical, optical or physical approaches; 2) invention of diagnostic, analytical, electronic devices with the exploitation of biological materials, cells, tissues or molecules.
We have being active and productive in several research areas. For example, we have developed flow-through ELISA lab-on-chip system. Its great potentials in various diagnostic applications have attracted interests from prestigious companies, such as BD and BIORAD, for commercialization. A novel microbial fuel cell, which boosts the power output by two folds comparing to the best performance reported up to date, is devised. Research on nanoparticle based nanomedicines is also actively undertaken with joint efforts with Singapore National Heart Center and School of Biological Science. In another line of our research, we are developing techniques for single molecule detections and single cell assays based on novel nanostructures such as nanopores, silicon nanowires, carbon nanotubes, and nano-electrochemical-electrodes. Optical sensing or imaging at both cellular and molecular levels is another aspect of our research endeavors.
Therapeutic engineering is a multidisciplinary field by nature. A wide range of experimental and conceptual approaches is often needed for new advances. It is, therefore, not surprising that faculty members are involved in research collaborations that go beyond department boundaries. Indeed, NTU has established close collaborative ties with Tan Tock Seng Hospital, the National Heart Center, the Singapore Eye Research Institute, the National Neuroscience Institute, the Genome Institute of Singapore, the Institute of Bioengineering and Nanotechnology; and overseas institutions such as Georgia Institute of Technology, MIT, Duke University and Shanghai Jiaotong University. Over the last two years, several lead PIs have filed several patents in related fields and published their works in many international scientific journals.
Our research covers a wide variety of areas vital to addressing key issues in the field of regenerative medicine:
• Cell and Tissue Engineering
Tissue engineering, a rapidly advancing field involving engineering and life sciences principles, offers the hope of changing traditional approaches to answer many crucial health care needs. We have been developing novel native-like scaffolds, biomaterials and bioreactors. The scope of research spans from musculo-skeletal tissue engineering, neural tissue engineering, stem cell engineering to cardiovascular tissue engineering. In the near future, many engineered viable tissues and organs may be potential candidates for engineering reconstruction, including blood vessels, peripheral nerves and cartilage. Complementing these efforts, more fundamental issues such as cell-matrix, cell-fluid flow interactions and stem cell differentiation are also being investigated.
• Molecular and Cell Physiology
Understanding the biophysical properties of cells on biomaterials is essential for designing new tissue regeneration processes and for developing new medical devices. Elucidation of the synergistic interplay between biochemical, physical and mechanical signals can be important for the regulation of cell adhesion, regeneration and recovery on biomaterials or extracellular matrix (ECM). Integrative bio-analytics are critical to our research. Using functional microscopy, optical tweezers and atomic force microscopy, we examine the biophysical dynamics of cell regeneration, biomechanics of membranes and dynamic adhesion of bacteria. We will devise important design principles for engineered tissue equivalents, bio-inspired materials and anti-microbial devices.
• Computational Biology
With the rapid availability of genetic and biological information, SCBE researchers draw on this data as we combine the knowledge of the human genome with the massive power of modern computers to construct simulations of human organs. We have used computational techniques to correlate intimal thickening in coronary artery bypass grafts and the dominating hemodynamic parameters. In the years to come, our simulation models will be so realistic that they can be used to design and test novel therapeutics, including medical implants, pharmaceuticals and clinical procedures.
Synthetic biology is an emerging scientific field, defined as “the design and construction of new biological parts, devices, and systems, and the redesign of existing, natural biological systems for useful purposes”. This emerging field aims to build artificial biological systems for engineering applications. More specifically, synthetic biology integrates science and engineering to design and synthesize novel biological components and functional systems that do not exist in the natural world. The main focus of synthetic biology research is currently on the process of characterizing natural biological systems, re-designing and fabricating them, and using them as engineered functional systems. So far, much emphasis has been placed on creating a general scientific and technical infrastructure that supports the design and synthesis of biological systems. For this purpose, synthetic biologists have implemented digital logics into cells so that biological functions can be translated into system design and operations. For instance, synthetic biologists attempt to (i) design standard biological parts that have defined performance properties, (ii) incorporate novel design methods and tools into engineering environment, and (iii) reverse- and re-engineer natural bacteria. Overall, synthetic biology possesses great potential to exploit the power of natural biological systems for engineering applications such as cost-effective production of biomedical drugs and energy-rich biomolecules.
Proteomics is an integration of the fields of biology, chemistry, physics and mathematics to elucidate protein functions in complex biological systems. Specifically, proteomics involves the identification, quantification and characterisation of all proteins involved in a specific pathway, cell, tissue, organ of organism that are studied in tandem, to provide accurate and comprehensive information about that biological system. Understanding the entire array of proteins expressed by a genome, cell, tissue or organism, the structure and function of each protein, and the complexities of protein-protein interactions will be critical to develop effective diagnostic techniques and disease treatments in the future. The analysis of proteomes is often more challenging and complex than genome sequencing because (i) proteins derived from a single gene can readily undergo post-translational modifications, and (ii) proteomes vary dynamically throughout the cell lifetime, thus require more complex analytical technologies compared to genome-based ones.
Most proteins function inter-dependently with other proteins, and identification of the way these proteins interact at atomic, molecular and/or cellular levels will provide knowledge on the functions of newly discovered proteins. The development of modern proteomics tools such as separation techniques coupled with high-throughput mass spectrometry technologies have expanded the scope of protein identification and quantification. Protein-protein interactions are now possible via protein microarrays, mass spectrometry, phage display and computational methods. Emergence of improved proteomics-based approaches will also advance biomarker discovery and development. Biomarkers are important for development of novel therapies, as well as improved disease prevention and treatment. The development of new proteomics technologies to sensitively detect low-abundance proteins and more specific methods will therefore facilitate validation of protein biomarker candidates, and allow assessment of therapeutic modes.
Proteomics aims to elucidate the way intracellular protein cascades change as a result of specific diseases, thereby identifying novel potential drug targets. It subsequently aims to validate particular drug candidates against those targets by providing information on how those drug candidates affect the proteome cascades. Therefore, in addition to providing answers to fundamental questions about the molecular basis of a cell's state, proteomics promises to accelerate novel drug and biomarker discovery through automated analysis of different molecular phenomena.
Nanomedicine & Gene/Drug Delivery
Nanomedicine aims to utilize nanotechnology in solving challenges in medicine at molecular scale. Molecular scale is in the order of nanometer (one billionth of a meter) to micrometer (one millionth of a meter). Current challenges range from early disease detection to delivery of therapeutics and tissue repair.
One of our School’s focuses is on the study and development of “nano” systems which are able to deliver therapeutic cargos such as drug or gene to specific parts of the body at a specific rate and amount. Our faculties apply integrated principles of nanotechnology, biology, and medicine on the development of nanocarriers made of polymeric particles, polyelectrolytes, proteins, and carbon-based structures, as well as drug-eluding stents and gene transfer methods in tissue engineering.
Injectible biodegradable and biocompatible polymeric particles like microspheres, microcapsules, nanocapsules and nanospheres are currently employed as controlled-release dosage forms. These polymeric devices avoid the inconvenience of surgical insertion of large implants. They generally release drugs by diffusion and/or by chemical mechanisms such as degradation of the polymer or the bonds between the drug and a polymer backbone. Particulate carrier systems can also be used for therapeutic growth factors delivery in tissue engineering. The delivery of drugs and/or growth factor utilizing different types of particulate systems with regards to the materials used and various modifications are investigated.
The fabrication and investigation of ultra thin organic films are of great interest in technology as well as in biotechnology. One technique for the preparation of nanometer-thick films on charged surfaces and colloids is based on differently charged polyelectrolytes, including the consecutive adsorption of biological macromolecules, surfactants, phospholipids, nano-particles, inorganic crystals and multivalent dyes. Polyelectrolyte microcapsules (PEMC) are produced by layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes onto the surface of colloidal particles or cells with subsequent core dissolution. These microcapsules can be produced with various polyelectrolytes including biodegradable materials in sizes ranging from about 100 nm to 10 m depending on the template used. The possibility of controlling their mechanical properties as well as the flexibility in the choice of constituents makes these capsules very promising for numerous applications in materials and life sciences. Besides the study of the mechanical and other physical properties, one of our main interests is to obtain a better understanding on how to incorporate biological functions into these micro and nano-composites and how to control their interaction with other cells. Our long term goal is to create artificial cell-like structures with well defined functions and physicochemical properties; such structures should have many potential uses such as drug delivery systems or as diagnostic tools.
Another area of interest is the applications of nanometer protein scaffold as drug/gene delivery vehicles. Protein possesses an inherent self-assembling ability to form nanoscale structure upon which functional groups can be attached. These functional groups serve as attachment points for drug/gene as well as targeting ligands. Once drug/gene is encapsulated within the scaffold and delivered to a particular tissue/organ, subsequent release of the drug/gene will be triggered by degradation or disassembly of the protein scaffold. Our interests are in investigating the external and internal factors that influence the protein scaffold self-assembly as well as ligand attachment, and release characteristics. This work will lay groundwork for future projects studying the incorporation of various molecules into protein scaffolds.
Drug-eluting coated and degradable stents offer an alternative to bare-wire stent and bypass grafting in the treatment of stenotic or atherosclerotic coronary disease. Our work involves developing numerical models and experimental studies to design more effective drug-eluting stents. A 2-dimensional model has been developed, coupling the effect of both blood flow in the lumen and transmural flow to the transport of drugs, to understand the local pharmacokinetics during the stenting procedures. We are currently developing improved models, taking into consideration the binding of drugs to tissues, to better illustrate the kinetics of drug-release, transport, binding, and absorption under the physiological states. In addition, we are developing models and experiments to understand the degradation of drug-loaded stent and the release of drugs, as well as the effects of fluid dynamics on the degradation of stent, delivery and distribution of drugs in the tissues.
Besides the above, investigations in combining gene transfer techniques and tissue engineering methods are also being developed. The aim is to develop engineered articular cartilage using chondro-progenitor/stem cells by co-culturing with autologous chondrocytes that are transfected with therapeutic growth factor genes. A sustained and localized growth factor presentation is pursued for promoting the cartilage healing in situ. The novelty and advantages of this strategy are highlighted by the introduction of co-culture system. It avoids directly transfecting the therapeutic progenitor cells, but transferring growth factor genes to their co-cultured cells. Therefore, the viability and chondrogenic specificity of the therapeutic progenitor cells can be maintained from the invasive gene transfection treatment. Additionally, a mechanism capable of timely turning off the over-expressed growth factor supply is also created. This design avoids the premature hypertrophy and apoptosis of the therapeutic cells, which is usually catalyzed by the overshot presentation of endogenous grow factors.
The potential of carbon-based materials, such as carbon nanotubes, as gene delivery vehicle is also being investigated.
Applying a multi-disciplinary approach, with integration of biosensing technology and engineered carrier to tissue engineering, we plan to develop ‘smart’ delivery devices in the future. The rationale is to enable the sensing of the presence of specific cells and the release of therapeutic molecules thereafter. This would increase the specificity to which therapeutic molecules are being delivered to. In addition, it would also reduce the potential of degradation of the therapeutic molecules before the cells are able to receive them.
People: Bjoern Neu, Chen Yuan, Chong Chuh Khiun, Ooi Chui Ping, Sierin Lim, Wang Dongan
Bioimaging has become an essential component in many fields of medical research and clinical practice. There is now a wide range of imaging techniques which are being used in basic medical science. These go from imaging techniques, such as Magnetic Resonance (MR) and Positron Emission Tomography (PET) that operate at the whole body level; to cryo-electron microscopy that can be used for imaging molecules, proteins, cells etc; to atomic force microscopy. Bioimaging allows structures and mechanisms of the human body to be examined from the whole body level to the molecular level. This is important in gaining understanding of disease in order to improve human health. The bioimaging group focuses on several areas of bioimaging. This includes the development of new non-invasive imaging modalities, novel materials for bioimaging, and bioimaging analysis and visualization methodology/techniques.
In the area of diffuse optical imaging, we attempt to develop a novel clinical imaging modality that is non-invasive, inexpensive, and comfortable. We use light in 650~900nm wavelength range that penetrates deeply into human tissue, in order to obtain tomographic map of physiological parameters such as blood volume, blood oxygen saturation, and scattering coefficient. Also, a correlation analysis of the fluctuation of the light transmission gives a relative blood flow information in deep tissue. Therefore, the diffuse optical imaging can help diagnosis and therapy monitoring of malignant tumor, especially breast cancer. Other application includes brain studies and muscle studies, as well as various animal model experiments.
In the area of materials development for bioimaging, we have successfully fabricated biocompatible inorganic fluorophores which have the advantages of sharp emission and long emission lifetime over organic fluorophores. These inorganic fluorophores are in nanosize range and can be functionalized for cell targeting. We have developed water-dispersible fluorescent and magnetic bifunctional nanomaterials, which show up-conversion fluorescent property and hence are suitable for deep tissue imaging. These materials also show superparamagnetic property. We envision such bifunctional fluorescent magnetic nanomaterials to have promising applications in simultaneous diagnostics (optical and magnetic)-cum-targeted therapy.
In the area of imaging analysis and visualization, we are developing medical image processing and visualization techniques that enable clinicians to study the disease in a fast and efficient manner using MRI. This is carried out in the context of Osteoarthritis (OA) which is the wearing of cartilage. Adequate visualization of cartilage is paramount in allowing accurate and clinically meaningful assessment of cartilage surface morphology and thickness. This includes developing image segmentation, registration and visualization methods. We are also developing multi-modal registration technique which allows the integration of different imaging modalities (e.g. optical imaging, electron microscopy etc), in order to visualize and study the disease state at the cellular and molecular levels. In the area of PET, we are devising methods to detect the smallest possible symptomatic malignant tumors at early stages and, in the context of screening, the smallest possible asymptomatic tumors. Information about asymptomatic tumors can be used to determine whether the tumor is a manifestation of a malignant or benign disease. This study is carried out in collaboration with Department of PET & Nuclear Medicine, Singapore General Hospital (SGH) which acquires images of patients having different types of tumor. The involvement of medical experts from SGH ensures the accuracy and efficiency of devised methods.
People: Poh Chueh Loo, Julian Chan CC, Kijoon Lee, Timothy Tan
Chiral and pharmaceutical engineering
Pharmaceuticals and Biomedical sciences have been identified as key engines of growth for the Singapore economy. In the recent years, Singapore has seen a strong growth in this sector with several major pharmaceutical players setting up manufacturing and research facilities. Pharmaceutical engineering research at the school of chemical and biomolecular engineering (SCBE), Nanyang Technological University (NTU), focuses on the development of synthetic routes, development of new processes and optimizing current industrial practices related.
A key area of focus is on chiral pharmaceuticals. Chirality, meaning handedness, is a central dogma in organic chemistry. Chiral compounds exist in two enantiomeric forms, which have identical molecular formula but whose structural arrangement form non-superimposable mirror images. Several pharmaceutical drugs are chiral in nature. In many cases, one enantiomer is the active pharmaceutical ingredient while the other can be benign or even toxic. Hence regulatory bodies enforce strict regulations for the manufacture of chiral drugs.
Our research focuses are in the following areas:
• Asymmetric synthesis of single enantiomers
• Development of chiral stationary phases for the separation of enantiomers
• Enantiomer separation by large scale chromatography, e.g. Design, control and optimization of simulated moving bed (SMB) processes, Supercritical fluid chromatography (SFC) etc
• Development of Enantioselective catalysts
• Crystallization process development and control