Post-doc.: Stanford University (USA)
Dr. es. sc. (equiv. Ph.D.): Swiss Federel Institute of Technology at Lausanne (EPFL, Switzerland)
Dipl. Phys. (Physics): University of Heidelberg (Germany)
The research in my group is directed towards biophysics with an emphasis on biophysical fluorescence. This highly interdisciplinary domain requires the interaction of chemists, physicists, and biologists. Only a concerted effort of these three groups will allow us to tackle the problems in the life sciences. The close proximity of departments of biology, biochemistry, chemistry, and physics at the National University of Singapore on one side and the research institutes (RIs) on the other side, allows us to develop physical and chemical methods for the study of biological questions on one hand and to apply these methods to the frontier in biology on the other hand. Our interests lie accordingly in the different areas that interact freely to advance this research field.
Construction and development of new optical tools. Optical Spectroscopy is one of the most sensitive tools available in the life sciences. Proteins can be studied not only in ensembles but as well on the single molecule level. Besides using well established methods in our group (e.g. Fluorescence Correlation Spectroscopy, Fluorescence Resonance Energy Transfer), we also plan to develop new spectroscopy and microscopy tools and new mathematical procedures to study proteins on a single molecule level in vitro and in vivo.
Study of selected proteins and protein complexes on a single molecule level and in living cells. In collaboration with the Department of Biological Sciences, the Department of Microbiology and the RIs we will study the properties of selected proteins and peptides to elucidate their function on a molecular level. At the moment we concentrate on either antimicrobial peptides and their interaction with bacterial membranes, or on the study of transmembrane proteins (G-protein coupled receptors, growth factors) and their structure, function and interactions.
One of the most interesting questions in biology is the relationship between the structure and function of proteins. With the fluorescence tools developed in our group we hope to shed some light on this question by in vitro experiments. In a complementary approach we will study the proteins in living cells because proteins are in many cases very sensitive to their environment and only when studied under physiological conditions can we determine their exact function.
Telephone: (+65) 6516 1248
Research Fellow: Mechanobiology Institute, Singapore
Ph.D., (Computation and Systems Biology): Singapore-MIT Alliance
B.Tech., (Industrial Biotechnology): Center for Biotechnology, Anna University, Chennai (India)
Understanding the diffusion properties of biofilms using fluorescent techniques.
Bacterial biofilms are communities of bacteria attached to a surface embedded in extracellular polysaccharides. In many cases, bacterial biofilms are found to be resistant to antibiotics. Currently, there are two different theories regarding the reasons for resistance. One of them is the presence of persistor cells which are known to be genetically altered and possess the antibiotic resistance genes. Another school of thought say that the extracellular polysaccharides surrounding the biofilm form a diffusion barrier to these antibiotics. It is plausible that the antibiotic resistance is conferred by a combination of both these mechanisms. The project aims to elucidate the contribution of physical mechanisms in conferring resistance to antobiotic for biofilms. This project is done in collaboration with SCELSE, Singapore Center for Environmental Life Sciences Engineering.
Research fellow: University of Strasbourg (UDS), Strasbourg, FRANCE; from 10/12 till 03/16
Research fellow: Case Western Reserve University, Cleveland, Ohio, USA; from 05/11 till 09/12
Ph.D., (Biophysics): University of Strasbourg (UDS), Strasbourg, FRANCE
M.Sc., (NanoScience): Amity University (AINT) (India)
B.Sc., (Life Sciences): Delhi University (India)
Revealing molecular events of the Dengue Virus during its infection process, its effect on the host cell, and its replication mechanisms by using Fluorescence spectroscopy and imaging techniques
Dengue Virus (DENV) is an enveloped RNA Virus that contains a 11 kb positive sense RNA as its genome and belongs to the family Flaviviridae. Despite its high clinical impact, little is known about the infectious cell entry/exit pathway. Recently, using live cell imaging techniques it has been shown that DENV particles are delivered to pre-existing clathrin-coated pits by diffusion along the cell surface. Consequently, due to membrane fusion with late endosomes, its viral content is released into the cytoplasm of host cell. Although earlier studies provide ample insight into the viral cell entry/exit mechanisms still the associated changes at molecular level within virus and the host cell are missing. I am interested in joining such missing links. To obtain this, different biophysical, bioimaging and biochemical techniques, like single molecule FRET, confocal FCCS, imaging FCS, anisotropy and time-resolved spectroscopy, will be used.
Teaching Assistant, Harvard University (USA)
Business Analyst, ExxonMobil Asia Pacific Pte. Ltd.
B.Sc. (Chemical Engineering): National University of Singapore
Study of biomolecular interactions in zebrafish model for spinal muscular atropy using fluroescence spectroscopy
Spinal Muscular Atrophy (SMA) is a genetic autosomal recessive neurodegenerative disease that is characterized by the loss of alpha motor neurons in the anterior horn of the lower spinal cord. This leads to progressive wasting of proximal muscles, paralysis and eventually death. With an incidence of 1 in 10 000 births and a carrier frequency of 1 in 35 people, SMA is the leading cause of genetic infant mortality. The disease-determining gene for SMA was identified to be the Survival Motor Neuron gene 1 (SMN1) in 1995.
One hypothesis suggests that the deficiency in SMN results in defective snRNP assembly and consequently aberrant splicing of selected genes in motor neurons. Another model suggests a neuron specific function of SMN important for mRNA transport for axonal outgrowth and neuromuscular junction development, in which a SMN-mRNA granule hypothesis has been proposed. In this model, SMN interacts with RNA binding proteins to form a RNP complex which is responsible for the localization of β-actin mRNA and possibly other transcripts to axons and the growth cone.
Currently, evidence on the interaction of SMN with its associated proteins for axonal transport is obtained by biochemistry experiments or co-localization studies in vitro or ex vivo. There has not been any in vivo study so far that can provide a direct evidence of a synchronized movement of SMN and its associated proteins and mRNA along the motor axons. Our lab, in collaboration with Christoph Winkler’s lab, is interested to study the dynamics of SMN and its associated protein quantitatively in the motor neurons of zebrafish in vivo using Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Cross Correlation Spectroscopy (FCCS).
B.Sc. (Chemistry): National University of Singapore
Single plane illumination microscopy (SPIM) based fluorescence correlation spectroscopy (FCS) (SPIM-FCS) is a multiplexed technique which utilizes the combination of plane illumination from a thin light sheet with fast array detectors such as an electron multiplying charged coupled device (EMCCD) to yield quantitative spatial maps of diffusion coefficient and concentration. The freedom to illuminate any plane of a 3D sample selectively by the SPIM illumination scheme provides an avenue to decipher the z-dependence and heterogeneity of molecular dynamics in the 3D sample upon performing SPIM-FCS measurements. I am applying this technique in model membranes, live cell membranes and live zebrafish in the context of the diffusion and organization of lipids and signaling proteins in vitro and in vivo.
M.Sc. (Biomedical Engineering): Imperial College London (UK)
B.Sc. (Physics): Aristotle University of Thessaloniki (Greece)
Developing optical methods for the characterisation and monitoring of bacterial biofilms along different stages of their life cycle
Biofilms are responsible of 80% of all bacterial infections and pose a risk to many domains in life. The mechanisms of their growth and colonisation are not completely understood, but have been connected to environmental cues. I am working on transient state (TRAST) monitoring in combination with Selective Plane Illumination Microscopy (SPIM) to reconstruct of 3-D maps of various metabolites that will reflect the complex architecture of the biofilms. Additionally, using Brillouin spectroscopy, I am studying the micromechanical properties. Such information will provide clues on how to influence biofilm growth and potentially inhibit or remove them.
BS-MS Dual Degree (Biological Sciences), IISER-Mohali (India)
Understanding the biophysical and structural basis of allosteric activation of Epidermal Growth Factor receptor using FCS and mass spectrometry
Epidermal growth factor receptor (EGFR) signaling is involved in diverse fundamental physiological processes such as cell proliferation and apoptosis. Upregulated tyrosine kinase activity of the EGFR/ErbB family is often implicated in a variety of human cancers. Even after decades of research on this signalling there are still gaps in our understanding of activation mechanism of EGFR at and across membranes. Most of the studies carried out on EGFR are on either extracellular or intracellular region of receptor but it is now speculated that transmembrane and juxtamembrane region of receptor are playing important roles in activation and regulation of EGFR signalling. Secondly, being an integral membrane protein EGFR actively interacts with its surrounding membrane environment but it is not well understood what are these interactions and how they affect the signalling. In order to fill some of the existing gaps in understanding of EGFR signalling in my project I plan to study the biophysical and structural basis of allosteric activation of EGFR signalling using Fluorescence Correlation Spectroscopy (FCS) and mass spectrometry. A combination of these two methods will provide information about lateral interactions crucial for EGFR signalling and allosteric changes taking place in the receptor across the membrane. This project will be done in collaboration with mass spectrometry focussed labs : Prof. Ganesh Anand Srinivasan's lab for structural mass spectrometry and Prof. Markus Wenk's lab for lipidomics.
B.Sc. (Chemistry-Computational): University of Colombo (Sri Lanka)
M.Sc. (Analytical Chemistry): University of Colombo (Sri Lanka)
Study of Dengue virus and infection using Fluorescence Correlation Spectroscopy
M.Sc(Integrated) Biological Sciences : BITS Pilani (Hyderabad Campus) , India
Study of development of zebrafish embryo using Light Sheet Imaging - Fluorescence Correlation Spectroscopy.
B. Tech. (Biotechnology): SRM University, Chennai (India
Investigation of membrane dynamics and organization of epidermal growth factor receptor (EGFR) by fluorescence methods