Structural Genomics

The Recent Progress of Structural Genomics in Taiwan [ 下載 PDF ]

Shan-Ho Chou

Structural genomics is a new and rapidly progressing research frontier. Together with the advances of genome sequencing and bioinformatics, it can make a significant impact toward the modern biotechnique and drug development. This article describes the recent progress in hardware and software in this area in Taiwan. Hopefully it will attract more researchers and students to jump into this wagon to speed up the development of this important sector.

Application of Bioinformatics in Structural Genomics [ 下載 PDF ]

Ping-Chiang Lyu, Yi-Chung Liu, Si-Ming Lai

The structural genomics project aims at determination of the 3D structure of all proteins experimentally and theoretically. Structural information of a protein is valuable in functional annotation and powerful in new drug-discovery. Another goal is to provide at least a representative structure for each protein family. Sequence and structure data will be combined using bioinformatics methods (a) to compare with the known data in the database, (b) to predict and analyze targets, (c) to help target selection, (d) and to provide a platform to communicate and coordinate.

NMR Structural Genomics of Klebsiella Pneumoniae [ 下載 PDF ]

Shih-Chi Luo, Yuan-Chao Lou, Sheng-Kuo Chiang, Yun-Ru Pan, Chin-Pan Chen

Based on the statistical analysis by the Department of Health, pneumonia is one of the top ten cases causing death every year in Taiwan. Klebsiella pneumoniae (KP) is one of the top five pathogenic bacteria that cause community and hospital infection of pneumonia in Taiwan. In some immunodeficient patients such as diabetic, KP forms opportunistic infection and causes septicemia combining with Pyogenic liver abscess. It is estimated that ~ 10% of these patients accompany meningitis and metastatic ophthalmitis. Recently, on the basis of the epidemiological investigations, the drug-resistant mutant genes of KP have been found due to the misuse of antibiotics, and even evolve into new strains which make lots of difficulties on therapies. It is therefore that the National Research Programs for Genomic Medicine (NRPGM) lists KP as one of the major bacterial researches that should be pursued. Our laboratory, a member of the KP functional and structural genomics projects of Academia Sinica, has selected several target proteins related to virulence and drug-resistance factors, as discovered by Dr. Shih-Feng Tsai in NHRI, for structural study. A variety of biophysical techniques, especially high-resolution NMR experiments, will be carried out on these target proteins. It is hoped that the 3D solution structures of these target proteins as well as other biophysical properties could provide valuable information for drug development on therapeutics related to Klebsiella pneumoniae.

The Structural Genomic Studies of Xanthomonas Campestris: A Plant Pathogenic Bacterium [ 下載 PDF ]

Shan-Ho Chou

This article mainly discusses the recent progress in structural genomics studies of the plant pathogen Xanthomonas campestris executed in the Institute of Biochemistry, NCHU. Structural genomics is a new and rapidly progressing research frontier including bioinformatics, NMR, X-ray diffraction, functional genomics, and proteomics, etc. If successfully executed, it can make a significant impact toward the modern life science, biotechnique and drug development. We have made a significant progress toward this goal, and believe that Taiwan Structural Genomics teams will make their its debut in future soon.

Current Status of Crystallography Beamlines and End Stations at NSRRC [ 下載 PDF ]

Chun-Hsiung Chao, Yuch-Cheng Jean

Protein crystallography is one of the most powerful and dominant tools to determine the threedimensional structures of biological macromolecules today. In order to increase the rate of crystal structure determination, the highly brilliant and easily tunable synchrotron radiation (SR) X-ray source is essential to meet the needs of abound structural information for studying structural genomics and structural-based drug designs. To satisfy these requirements, the National Synchrotron Radiation Research Center (NSRRC) has constructed two dedicated Synchrotron Radiation Protein Crystallography Facility (SPXF) high-throughput beamlines for structural genomics research. One of the beamlines will be a multi-wavelength anomalous diffraction (MAD) beamline with energy tunability from 6.5 keV to 19 keV for unknown structure determinations, and the other will be a monochromatic (mono) beamline with energy from 12 keV to 14 keV for crystal screening, drug design and high-resolution structure studies. The well-developed light source technique, advanced area detectors, high-efficient computing and network environments, automatic crystal sample changing and centering, and user-friendly data collection and control systems will produce 800 MAD data set per year for MAD beamline and 1200 useful data sets per year for mono beamline.

Recent Advances in Phasing Techniques for High-Throughput Macromolecular X-Ray Crystallography [ 下載 PDF ]

Chia-Wang Chiang, Yi-Ching Li, Li-Ying Lin, Tung-Ju Hsieh, Nei-Li Chan

X-ray crystallography is the most effective and widely used tool in determining the high-resolution three-dimensional structure of biomacromolecule. Key steps of this technique include purification and crystallization of target molecule, collection of X-ray diffraction data, phase determination for each reflection, and construction of a structural model followed by rounds of model refinement. Among them, crystallization and phase determination were known to be the main bottlenecks. With the recent instrumentation advances in crystallographic beamlines, the tunability of synchrotron radiation combined with crystals containing anomalous scatterers allow rapid phase determination by the method of multiple-wavelengths anomalous diffraction. This article introduces the theory and experimental procedure of this revolutionary phasing technique.

X-Ray Diffraction and Nuclear Magnetic Resonance in the Structural Genomics Study of Helicobacter Pylori [ 下載 PDF ]

Jya-Wei Cheng, Yuh-Ju Sun

The three-dimensional structure of protein is an essential topic for the biochemical function research in recent year. X-ray diffraction and nuclear magnetic resonance (NMR) are two important methods in this field. In this article, we will introduce the principles and circumstance of these two methods, and how we apply these two methods in our study: Helicobacter pylori structural genomics research. Proteins carry out their biological functions only when they fold correctly. A unique protein folding respects to have a specific biological function. So, we can investigate the three-dimensional structure of protein to study the possible biological function of protein. We determine the active site of protein and the key residues involved in the biological function. The resolution of these methods is in atomic resolution.

Membrane Protein Structural Biology [ 下載 PDF ]

Che Ma

Membrane proteins are an important class of proteins. They are essential components for cellular functions and processes; they play important roles as ion channels, transporters, enzymes and receptors. Their normal functions are fundamental to our health, and many impaired membrane proteins have been linked to serious diseases. Recent advances in the field of structural biology have enabled us to have better understanding of membrane protein structures. The three-dimensional atomic resolution structural information of membrane proteins is critical to understand their function and mechanism.

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Ultra-Precision Machining Technology [ 下載 PDF ]

Wei-Yao Hsu, Ching-Hsiang Kuo, Fong-Zhi Chen

Instrument Technology Research Center (ITRC) has devoted to limited and diversified ultraprecision components fabrication for more than 30 years, and established various aspheric optics fabrication units, precision centering machines, and micro lens and diffractive optical element (DOE) machining devices in the past years. To match up the massive growth of the optical industrial in Taiwan, ITRC introduced a new 5-axis ultra-precision machine in 2005. This machine has both single point diamond turning (SPDT) and ultra-precision grinding capability, and could fabricate both rotational symmetric and 3D freeform components. This article is focused on the ultraprecision machine technology, and SPDT and ultra-precision grinding technologies.

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Stray Light Analysis and Suppression in Optical System [ 下載 PDF ]

Cheng-Fang Ho, Ting-Ming Huang, Senq-Tsong Chang

Stray light are the unwanted light in optical system, it will reduce contrast or image quality. Sometimes, it will cause the mission fails. The stray light in optical system is always being there, but we can control the stray light in a reasonable order by a suitable opto-mechanical design. This article presents some basic concepts of stray light, the analysis of stray light suppression, and an analysis result of real case.

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Computer Simulation for the Fabrication of Hexagonal Micro Lens Array by Using Dragging Process with Excimer Laser [ 下載 PDF ]

Shuh-Yi Wang, Chun-Chin Huang

A computer simulation for the fabrication of aspheric hexagonal micro lens arrays by use of the laser dragging process was examined. In this new process, the first step is to generate micro channels whose cross-section shape is similar to that of the mask. Then the dragging procedure is repeated twice, each time after rotating the work piece by 60 deg relative to the previous channels. This hexagonal micro lens array may be applied in the application of image processing. Our results indicate that the hexagonal micro lens array has a better axial symmetry and higher fill factor than a rectangle one.