B.sc.(Microbiology), Ph.D.(Molecular Genetics and Genetic Engineering)
Macromolecular interactions play a major role in cellular regulation and biological function. Molecular recognition is one of the most important regulatory elements, as it is often the initiating step in reaction pathways and cascades. Malfunction of the specific proteins in the cascades may cause the serious disease problem. In addition, molecular recognition also plays fundamental roles in the regulation of gene expression, cellular metabolism, and drug design.
Atomic Force Microscopy (AFM) is a surface-sensitive instrument capable of imaging biological samples at nanometer resolution in all environments including liquids. Therefore, it is gaining rapid acceptance in the field of structural and molecular biology. AFM studies on DNA, RNA, protein, lipid, live cells and subcellular structures in different biological buffers can give detailed structural information in the native environment. When combined with immunofluorescence (single molecule fluorescence, nonashell tracking particle) and electrophysiology, AFM could become a powerful tool to study the structure-function relations of cell membrane protein and channels. With this high potential, it can also detect single molecules on cells surfaces generating chemical maps profile with nm resolution and single molecule sensitivity. Diagnostic in living cells is also possible to perform.
The potential of the AFM in detecting ultra-low forces at high lateral resolution has opened the exciting perspective of measuring molecular recognition at the single molecule level (nano-scale resolution), and in real time. The AFM results can be complemented by dynamic atomistic models using molecular dynamics simulation (MDS). These techniques can be applied to several studies, for example, the protein-protein interaction of enzyme-substrate complex and the inhibition studies are also possible. Drug design and commercial disease-kit-test development are major benefit with these tools. Moreover, establishment for Nanosensor tool and lab on chip are also very interesting.
We have established a collaborative research group among physiology, surface chemistry, biochemistry and atomic force microscopy, etc., within Thailand and oversea, in order to focus on molecular recognition studies. We have been investigating on sodium-glucose co-transporter SGLT1 expressed protein on the cell-lines surface. This protein facilitates the translocation of glucose into cells driven by the Na+ electrochemical potential difference across the membrane. The topology, glucose-binding pocket and stereospecificity of substrate transport of SGLT1 investigated by using biochemical and biophysical approached have been performing. In the near future, substrate- transport measuring by using Fluorescence Resonance Energy Transfer (FRET) will be developed. From these skills, we plan to pave a way for several biological research interests, especially, the problem-based in Thailand.
Department of Biology, Faculty of Science, Mahidol University
Rama VI Road, Rachadhavi, Bangkok 10400 Thailand