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Research and Development
Biomedical Engineering Lab –PI: Dr. Chih-Sheng Lin
- Studying the molecular mechanism of fibrotic remodeling in the hearts with cardiovascular disease: In heart, a proper balance between synthesis and degradation of extracellular matrix (ECM) is most importance in maintaining normally physiological functions. Prolonged production of several cytokines induced by tissue injury can lead to excessive ECM accumulation and chronic fibrosis, often resulting in organ failure. The interplay of matrix metalloproteinases (MMPs), a family of proteolytic enzymes responsible for ECM degradation, and its naturally endogenous inhibitor TIMPs have been demonstrated to play a pivotal role in ECM remodeling processes. In our laboratory, we performed the new insights into the underlying molecular mechanisms involved in ECM remodeling and showed that the pathological imbalance of MMPs and TIMPs causing abnormally accumulating ECM and fibrotic lesions in the heart failure, and also in pathological atria with atrial fibrillation.
- Fabricating biosensing systems for pathogen detection in clinical and food: The field of biosensor has grown rapidly in recent years. The biosensors of detecting virus infection and bacterial contamination have also been developed. In our laboratory, disposable amperometric detection strips were fabricated for the rapid detection of Dengue virus and E. coli O157:H7. In the study, we fabricated detecting system on screen printed carbon electrodes (SPCE) which are immobilized gold nanoparticles (AuNPs) on the working electrode to significantly enhance the detection sensitivity and limit.
- Using microalgal technology for carbon dioxide reduction and biodiesel production: Photosynthetic organism, microalgae, can efficiently use solar energy to combine water with CO2 to create biomass. Moreover, high oil-producing microalgae can be used to produce biodiesel. Microalgae have higher proliferation rate and superior efficiency in using CO2 for photosynthesis, and can be more readily incorporated into engineered systems. Furthermore, microalgal technology provides a means for recycling waste carbon from fossil fuel combustion. Therefore, in our laboratory, the main aims of research are the design and application of photobioreactor, and producing biodiesel from high lipid-content algae utilizing waste CO2.
Clinical-Biochemical Engineering Lab –PI: Dr. Jen-Tan Mao
Functional role of Haptoglobin in Atherosclerosis
Haptoglobin (Hp) is an acute-phase protein, with its plasma levels increasing consistently in response to infection and inflammation. Due to the existence of two different alleles (Hp1 and Hp2) in chromosome 16q22, three main Hp phenotypes exist: Hp1-1, Hp2-1 and Hp2-2. Apparently, the structural difference among the Hp types may drastically affect its biological function and clinical outcomes. So far, we have developed Hemoglobin affinity and monoclonal antibody affinity columns for purifying Hp from human plasma as reported in Protein Expression and Purification and Journal of Chromatography B, respectively. In our previous results, Hp was found to possess an extremely potent antioxidant activity (5 times greater than that of probucol, a well-known potent antioxidant), this finding was a critical milestone in currently related areas and has been published in Proteomics in 2004. Of remarkable interest, the antioxidant activity of the Hp β subunit was extremely potent and markedly greater than probucol (15X). Using a recombinant Hp, we demonstrate that the Hp β chain is an extremely potent antioxidant directly preventing LDL from oxidation as published in Protein Expression and Purification, 2007. It is conceivable that expressed β subunit may provide as an initial utility for the future design of “mini-Hp” for a potent antioxidant. In the clinical study, we established an ELISA assay to determine the phenotypes of Hp in plasma and the pure Hp 1-1, 2-1, and 2-2 were used as standards (Clinical Biochemistry in 2007). By collaborating with the Cardiology Division of Veterans General Hospital at Taipei, 1,200 subjects have been investigated to study whether or not Hp phenotype is associated with the risk in incident coronary artery disease (CAD). Using stepwise logistic regression analyses with the plasma apoA-I levels adjusted to determine the major risk factors, our data suggested that Hp 1-1 was associated with the risk of CAD by 2 times greater than Hp 2-1 and 2-2. Moreover, we are excited by finding the existence of a point deletion in Hp allele 1 mRNA present in all phenotypes of human samples. The deletion mutation resulted in the formation of a stop codon. To our best of knowledge, the existence of this truncated mRNA has never been reported and the critical report is almost done and ready to submit.
Physiological role of milk β-lactoglobulin
β-Lactoglobulin (LG) is one of the major milk whey proteins, containing about 10% of the total protein by weight. The molecular mass of LG is 18.5 kDa belonging to the lipocalin family. The secondary structure, it consists of nine β strands and one alpha-helix. The central hydrophobic pocket (calyx) possesses the property of binding to vitamin D, vitamin A, and fatty acids. LG is quite sensitive to thermal denaturation; the secondary structure is altered upon the heating with a transition temperature at 70-80°C. In the last five and half years, we have constructed a detailed thermal denaturation curve for LG with its time and temperature, the data providing the dairy industry with a valuable reference (Journal of Dairy Science, 2005). We have also mapped out a specific amino acid sequence region that is responsible for the thermal change above 80 °C. Such changes also result in losing its ligand binding abilities (retinol and palmitic acid) (Journal of Biological Chemistry, 2004). In addition, we have reported that a monoclonal antibody can only recognize the native form of LG, so that the un-denatured LG content in the processed milk can be determined (Journal of Dairy Science, 2004 and 2006). We showed that LG is a mild antioxidant whose potency is less than that of vitamin E and probucol (the latter being an antioxidant used for clinical therapy). The conversion of the LG monomer to dimer was responsible, in part, for the mode of action in protecting low-density lipoproteins against copper-induced oxidation (Journal of Dairy Science, 2007). More recently, we have shown that LG dramatically stimulates the proliferation of hybridoma B cells, but thermal denaturation abolishes this ability of LG. It is an important observation that the LG receptor was identified as a membrane Ig M using mass spectrum. We identified first the second vitamin D binding site of LG using synchrotron X-ray in National Synchrotron Radiation Research Center (NSRRC) (PROTEINS: Structure, Function, and Bioinformatics, 2008).
Mechanism involved in instant browning reaction over post-harvested fruit
Plant polyphenol oxidase (PPO), also known as tyrosinase in animals (EC 188.8.131.52), is an enzyme containing copper that catalyzes two different reactions using molecular oxygen, hydroxylation of monophenols to o-diphenols and oxidation of the o-diphenols to o-quinones. This enzyme, responsible for melanization in animals and for browning in fruits and vegetables, is widely distributed in microorganisms, animals, and plants. We developed a rapid gel-electrophoretic blotting technique to identify the possible molecular form of PPO on a dried chromatographic paper that was immobilized with a colorimetric substrate catechol (Journal of Chromatography B, 2007). The method also allows us to identify potentially potent inhibitors from natural products. Furthermore, in view of recent studies indicating that tyrosinase is responsible for hyperpigmentation in humans, tyrosinase inhibitors have become increasingly important in medical and cosmetic products. We show the presence of a potent volatile inhibitor(s) for PPO in litchi pericarp. The surface of post-harvesting litchi pericarp revealed an opening ultra structure under the scanning electron macroscopic examination, therefore allowing an instant evaporation of PPO inhibitor. As such, the PPO oxidation was proceeded. The novel finding clarifies the mechanism involved in the rapid browning phenomenon of post-harvesting litchi pericarp.
Bio-computational Lab – PI: Dr. Jenn-Kang Hwang
CELLO-- protein subcellular localization predictor
pKNOT -- the first knotted protein server
Intelligent Computing Lab – PI: Dr. Shinn-Ying Ho
- We aim to develop various evolutionary computation algorithms and optimization methodologies, and provide user-friendly tools for system optimization. A representative paper is as follows: S.-Y. Ho*, L.-S. Shu and J.-H. Chen, "Intelligent Evolutionary Algorithms for Large Parameter Optimization Problems," IEEE Trans. Evolutionary Computation, vol. 8, no. 6, pp. 522-541, Dec. 2004. (Highly cited article)
- Based on the expertise of intelligent computation, we develop various bio-inspired optimization algorithms for computational proteomics, computational systems biology, computational biology, bioinformatics, etc.
- We establish national/international interdisciplinary collaboration with biologists to investigate systems biology and validate our proposed models.
- We are interested in establishing a user-friendly system of computer-aid vaccine design.
Enzyme and Protein Engineering Lab –PI: Dr. Yuh-Shyong Yang
- Professor Yuh-Shyong Yang’s research interests involve in two distinct disciplines, biochemistry and electronics. He has focused on the collaborative integration of biochemical reactions and electronic devices. In particular, he is interested in how specific interaction between biomolecules may affect electronic response from semiconductor devices. During the past five years, his research accomplishments in the bioelectronics involve in using IC design, CMOS base devices and nanoelectronic devices for biochemical analysis and for ultra high sensitivity biosensing. In the biochemistry area, he is interested in the exploration of enzyme mechanisms and their biological significance. Specifically, he studies the biological sulfation and desulfation that regulate a variety of biological functions at molecular level and investigates the metal effects on enzyme actions.
Applied Microbiology & Biochemistry Lab –PI: Dr. Ching-Ping Tseng
Biotreatment of Waste Gas using Immobilized-Cell Reactors
Prof. Ching-Ping Tseng and his team at National Chiao Tung University Department of Biological Science and Technology have successfully isolatrd active microorganisms from sludge that are most efficient at deodorizing waste gas. They designed a circulatory bioreactor system that can replace the tradutional saw dust or washing tower methods used at composting plants or animal farms. This is a clean and environmental friendly process that not only improves deodorization efficiency but also reduces secondary pollution.
Bioinorganic & Bioanalytical Chemistry Lab –PI: Dr. Cheng Chang
- Most Cited Papers (> 80 citations; since 1979, total 108+ papers, SCI h-Index = 26, total impact factors > 320; total citations > 2040; average SCI citations per paper = 20, average SCI citations per year = 68.): 1. C.A. Chang*, H.G. Brittain, J. Telser, and M.F. Tweedle. "pH Dependence of Relaxivities and Hydration Numbers of Gadolinium(III) Complexes of Linear Aminocarboxylates", Inorg. Chem., 1990, 29, 4468-4473. [SCI: 4.123; Rank: 4/43; No. of Citations: 84 ] 2. M.F. Tweedle, J.J. Hagan, S. Mantha, K. Kumar, and C.A. Chang. "Reaction of Gadolinium Chelates with Endogenously Available Ions", Mag. Reson. Imaging, 1991, 9, 409-415. [SCI: 1.486; Rank: 47/87; No. of Citations: 85] 3. K. Kumar, C.A. Chang, and M.F. Tweedle. "Equilibrium and Kinetic Studies of Lanthanide Complexes of Macrocyclic Polyaminocarboxylates", Inorg. Chem., 1993, 32, 587-593. [SCI: 4.123; Rank: 4/43; No. of Citations: 102] 4. C.A. Chang*, L. Francesconi, M.F. Tweedle, et. al. "Metal Complexes for Magnetic Resonance Imaging: Synthesis and Characterizations of Fe(DO3A), Na[Fe(DOTA)], Gd(DO3A), and Na[Gd(DOTA)]", Inorg. Chem., 1993, 32, 3501-3508. [SCI: 4.123; Rank: 4/43; No. of Citations: 150] 5. C.A. Chang*, L.Francesconi, D. Dischino, M. Malley, J. Gougoutas, and M.F. Tweedle. "Synthesis, Stability, and Structures of Gd(III) and Y(III) Macrocyclic Polyaminocarboxylates". Inorg. Chem., 1994, 33, 3567-3575. [SCI: 4.123; Rank: 4/43; No. of Citations: 130]
BioXGEM – PI: Dr. Jinn-Moon Yang
- Our research focuses on computer-aided drug discovery and structural bioinformatics. We have developed a molecular docking tool (namely GEMDOCK) which is one of wide-used docking tools in the world. We cooperated with 10 research teams on diverse drug targets and experimental results demonstrate that our tools are useful for discovering lead compounds (e.g. dengue virus envelop protein, skimate kinases, and influenza virus neuraminidase), identifying functional sites (e.g. ß-lactoglobulin), and protein engineering (e.g. endo-chitosanase to exo-chitosanase). We published 7 papers on top journals in these fields and these papers were cited over 70 times since 2004. We get the 2007 National Innovation Award due to the achievement of iGEMDOCK which is graphic interface of GEMODCK. The iGEMDOCK was downloaded over 1,200 times and was used for education.
- For structural bioinformatics, we have achieved successful results on protein structure prediction (PS2), fast protein structure search (3D-BLAST), and structural protein-protein interaction networks (3D-partner). These results were published on the top journals (such as Nucleic Acids Research and Genome Biology) in these fields. A particularly exciting success is the development of the 3D-BLAST which is as fast as BLAST and has the features of BLAST (e.g. robust statistical basis, and effective and reliable search capabilities) for protein sequence search. 3D-BLAST is the first tool to search large protein structures (> 30000) within 3 seconds in the world. We believe that 3D-BLAST will be the most popular tool to elucidate the structural homology by large protein structure database search. The number of accessing this tool exceeds 5,100 from 44 countries and our papers were cited over 13 times since 2007.
Electrocardiology and Cardiovascular Bioinformatics Lab –PI: Dr. Ten-Fang Yang
Time Domain and Frequency Domain Signal Analysis in SAECG,
Time Domain and Frequency Domain Signal Analysis in HRV.
SAECG research in Normal Taiwanese,
HRV research in Normal Taiwanese,
Age, Gender and Race Variations on SAECG,
Age, Gender and Race Variations on HRV,
SAECG research on Hemodialysis Chronic Renal Failure Patients,
HRV research on Hemodialysis Chronic Renal Failure Patients,
Standard 12-lead ECG research on Heart Diseases,,
VCG and Derived VCG research in Cardiology,
Parametric Modeling of Signal averaged ECG,
Electrocardiological evaluation of Sudden Cardiac Death.
Lab – PI: Dr. Yun-Ming Wang
2007 Joint Annual Meeting ISMRM (International Society for Magnetic Resonance in Medicine)-ESMRMB (European Society for Magnetic Resonance in Medicine and Biology) 2007 Poster Award 3rd place
- Synthesis, Complexation and Water Exchange Properties of Gd(III)–TTDA–Mono and Bis(amide) Derivatives and Their Binding Affinity to Human Serum Albumin, Dalton Trans., 2749-2759, 2007. (Selected as Journal Cover)
With the objective of tuning the lipophilicity of ligands and maintaining the neutrality and stability of Gd(III) chelate, we designed and synthesized two bis(amide) derivatives of TTDA, TTDA-BMA and TTDA-BBA, and a mono(amide) derivative, TTDA-N-MOBA. The stability constants of TTDA-mono and bis(amide) complex are significantly lower than those of TTDA and DTPA, but the selectivity constants of these ligands for Gd(III) over Zn(II) and Cu(II) are slightly higher than those of TTDA and DTPA. From the 1H NMR titrations, the identification of the protonation site of the amide ligand shows that the first protonation site occurs on the central nitrogen atom. The simultaneous treatment of 17O NMR data is used to obtain many parameters affecting the proton relaxivity of Gd(III) complexes. It is found that the replacement of one carboxylate group by an amide group decreases the water-exchange rate of the gadolinium(III) complexes by a factor of about 5, and the trend is similar to those of DTPA and DTPA-bis(amide) derivatives. Furthermore, from the relaxivity and ultrafiltration studies, it is clear that the bound relaxivity (r1b) values of [Gd(TTDA-N-MOBA)(H2O)]/HSA and [Gd(TTDA-BBA)(H2O)]/HSA have remarkably high value. In addition, the increase of lipophilicity and non-covalent binding affinity with HSA of TTDA-mono and bis(amide) Gd(III) chelates increases the association constants for the binding of Gd(III) chelates to HSA.
Synthesis and Characterization of a New Bio-activated Paramagnetic Gadolinium(III) Complex [Gd(DOTA-FPG)(H2O)] for Tracing Gene Expression, Bioconjugate Chem. 18, 1716-1727, 2007. (Selected as Journal cover)
A smart contrast agent for magnetic resonance imaging (MRI) can be used to exploit an enzymatic activity specific to the tissue or disease state signified by converting an MRI-inactivated agent to an activated MRI agent. In this study, a ß-galactopyranose-containing gadolinium(III) complex [Gd(DOTA-FPG)(H2O)] was designed, synthesized and characterized as being potentially suitable for a bio-activated MRI contrast agent. The rotational correlation time value of [Gd(DOTA-FPG)(H2O)] is dramatically longer than that of [Gd(DOTA)(H2O)]. Relaxometric studies show that the percentage change in the T1 value of [Gd(DOTA-FPG)(H2O)] decreases dramatically in the presence of ß-galactosidase and human serum albumin.
The signal intensity of the MR image for [Gd(DOTA-FPG)(H2O)] in the presence of human serum albumin and ß-galactosidase (2670 ±210) is significantly higher than that of [Gd(DOTA-FPG)(H2O)] in the sodium phosphate buffer solution (1490 ± 160). In addition, the MR images show a higher intense enhancement in CT26/ß-gal tumor with ß-galactosidase gene expression but not for the CT26 tumor without ß-galactosidase gene expression.
Bioinformatics Algorithm Lab– PI: Dr. Chin Lung Lu
Multiple Sequence Alignment with Constraints (MuSiC, MuSiC-ME, RE-MuSiC)
We are the first to propose the concept of constrained sequence alignment that allows biologists to incorporate their knowledge about structures/functionalities/consensuses of their datasets into sequence alignment. By specifying known functionally, structurally or evolutionarily related residues/nucleotides of the input sequences as constraints, the output of the constrained sequence alignment is an optimal sequence alignment in the condition that the user-specified residues/nucleotides should be aligned together in the alignment, so that the output alignment can more accurately reflect the true biological relationships among the input sequences. In this study, we have first designed an efficient algorithm for computing a constrained alignment of multiple sequences and have also developed a web server, called MuSiC (Multiple Sequence alignment with Constraints), for the online analysis. Using MuSiC, we have successfully located the subsequence fragment of the RNA sequence of SARS that is capable of folding itself into a stable RNA secondary structure with pseudoknot responsible for the replication of SARS viruses (Bioinformatics, 20:2309-2311, 2004). Then we have further developed its memory-efficient version, called MuSiC-ME (Memory-Efficient Multiple Sequence alignment with Constraints), that allows the users to align multiple sequences of length up to several thousand residues (Bioinformatics, 21:20-30, 2005). More recently, we have developed RE-MuSiC by further enhancing the constraint formulation of MuSiC as regular expressions, which is convenient in expressing many biologically significant patterns like those collected in the PROSITE database, or structural consensuses that often involve variable ranges between conserved parts. Experiments demonstrate that RE-MuSiC can be used to help predict important residues and locate evolutionarily conserved structural elements (Nucleic Acids Research, 35:W639-644, 2007).Figure 1: Three GST (Glutathione S-Transferase) proteins: The structural similarity between these three proteins is very high, but their pairwise sequence identities are extremely low.
Figure 2: The constrained sequence alignment produced by RE-MuSiC, using the pattern of "[ST]-x(2)-[DE]" as the constraint, in which the residues shaded in yellow match the pattern. In addition, the residues in green boxes that correspond to the active sites shared by these three GST proteins are aligned together.
Research and Application of Biological Macromolecules Lab –PI: Dr. Tiao-Yin Lin
Effects of mutations on the electron transport catalyzed by thioredoxin reductase.
Molecular regulation Lab–PI: Dr. Hwei-Ling Peng
Bioorganic and Molecular Evolution Lab–PI: Dr. Tung-Kung Wu
The structure-function-mechanism and molecular evolution studies of oxidosqualene cyclase enzymes: Our goals in this project are to gain in-depth insights of how cyclase enzymes catalyze the complex cyclization/rearrangement reactions during sterol and triterpene biosynthesis that have captivated chemists and biochemists for more than half a century, and to develop novel inhibitors of these enzymes for potential use as antifungal, hypocholesterolemic, and phytotoxic agents. In parallel, promiscuous residues of cyclase enzymes is subjected to protein engineering to study product specificity/diversity during the molecular evolutionary course of the cyclases. We have identified several important amino acid residues involved in the enzyme catalysis and substrate binding. Numerous truncated intermediates have also been isolated to directly demonstrate the function of the amino acids to the mechanism of the oxidosqualene cyclization/rearrangement cascade.
The Research on the biosolar energy device design and biomass-directed renewable energy production: Our goals here are to use materials from organic, organometallic, nano-particles, and bio-molecules and integrate them into a biosensitized solar cell device for the conversion of solar energy into electric or chemical energy. Specifically, protein will be subjected to protein engineering to obtain mutants with altered or improved electron transfer activity and tested for biosolar energy conversion efficiency. In parallel, results from the ultrafast relaxation dynamics showed profound effects of the protein matrix on the prosthetic group in different environments. We have successfully demonstrated the first example of biosensitized solar cell made with artificial proteins as potential photosensitizers and opened up a new avenue for the design and development of new biosensors, photo-electrocatalysts, or bio-mimetic solar cells.
Molecular Genetics Lab – PI: Dr. Yun-Liang Yang
- Discovering that drug resistance and morphogenesis/virulence both are under the regulation of Efg1 and Cph1, two known virulence factors in Candida albicans.
- Unveil the involvement of glycolytic enzymes in the morphogenesis/virulence pathway.
- Identification of the first anti-dengue drugs in cell culture system.
The Cell Biology and BioChip Lab–PI: Dr. Chiun-Jye Yuan
Molecular mechanism study of Mst3-mediated cell apoptosis
Mst3 was found to be present in the mitochondrial intermembrane space, where it may associate with pro-apoptotic proteins, AIF and endonuclease G (EndoG). In mitochondria, Mst3 was postulated to regulate the activity of pro-apoptotic proteins and/or the associated DNase in response to the apoptotic stimuli, such as oxidative stress and staurosporine.Fig. 1 The endogenous Mst3 (thread-like green fluorescence) was found to partially colocalize with Mitotracker (red), a mitochondrial specific fluorescent dye, and red fluorescent signals of AIF and EndoG (yellow/orange signal).
Elucidate the role of Mst3 in normal spontaneous delivery
We demonstrated for the first time that Mst3 plays an essential role in the apoptosis of trophoblasts during normal spontaneous delivery. Oxidative stress, but not hormones released during labor such as prostaglandin E1, oxytocin or angiotensin II, induces the expression of Mst3 and apoptosis of human term placenta during labor (Fig. 2). Further studies showed that Jun N-terminal kinase (JNK) may participate in the signaling pathway of H2O2-induced apoptosis by mediating the level of Mst3.Fig. 2. Human tissue specimens were placenta from spontaneous delivery (a-d), selective Cesarean section (e-h) and fetal membrane of first trimester (i-l). Mst3 expression (a,e,i); apoptosis signals (b,f,j); nitrotyrosine (c,g,k) and caspase3 activations (d,h,l were indicated).
Development of bio-nanodevices for cancer therapy
An novel horseradish peroxidase (HRP)-encapsulated silica nanoparticles (HRP-SNP) was developed in our laboratory with an average size of around 100 nm for the application of cancer therapy (Fig. 3). HRP was demonstrated to catalyze the conversion of non-toxic prodrug indole-3-acetic acid (IAA) into toxic products for cancer therapy. Further studies showed that the developed HRP-SNP was nontoxic to HeLa cells without IAA; whereas, in the presence of IAA, the viability of HeLa cells decreased rapidly in a time- and dosage-dependent manner.
Fig. 3. TEM of the developed ESNP.
Nano-Biotechnology Lab–PI: Dr. Chia-Ching Chang
Self-assembled molecular magnets on patterned silicon substrates: Bridging bio-molecules with nanoelectronics
The paper reports the methods of preparing molecular magnets and patterning of the molecules on a semiconductor surface. A highly magnetically aligned metallothionein containing Mn and Cd (Mn,Cd-MT-2) is first synthesized, and the molecules are then placed into nanopores prepared on silicon (0 0 1) surfaces using electron beam lithography and reactive ion-etching techniques. We have observed the self-assemble growth of the MT molecules on the patterned Si surface such that the MT molecules have grown into rod or ring type three dimensional nanostructures, depending on the patterned nanostructures on the surface. We also provide scanning electron microscopy, atomic force microscopy, and magnetic force microscope studies of the molecular nanostructures. This engineered molecule shows molecular magnetization and is biocompatible with conventional semiconductors. These features make Mn,Cd-MT-2 a good candidate for biological applications and sensing sources of new nanodevices. Using molecular self-assembly and topographical patterning of the semiconductor substrate, we can close the gap between bio-molecules and nanoelectronics built into the semiconductor chip.
Laser induced popcornlike conformational transition of nanodiamond as a nanoknife
Nanodiamond (ND) is surrounded by layers of graphite on its surface. This unique structure feature creates unusual fluorescence spectra, which can be used as an indicator to monitor its surface modification. Meanwhile, the impurity, nitroso (C-N=O) inside the ND can be photolyzed by two-photon absorption, releasing NO to facilitate the formation of a sp3 diamond structure in the core of ND and transforming it into a sp2 graphite structure. Such a conformational transition enlarges the size of ND from 8 nm into 90 nm, resulting in a popcorn-like structure. This transition reaction may be useful as nano-knives in biomedical application.
1. SEM images of the A549 cell lines, irradiated with/without laser following ND treatment.
2. SEM image of 6 nm nano-diamond before and after laser radiated. The average size of laser radiated nano-diamond is about 90 nm.
Integrative Systems Biology Lab – PI: Dr. Hsien-Da Huang
[MicroRNA Regulation: Databases and Tools]
Recent works have demonstrated that microRNAs (miRNAs) are involved in critical biological processes by suppressing the translation of coding genes. In order to facilitate the investigation of microRNA regulation, we developed several biological databases and computational tools in this important field. Six articles in this filed were published in Nucleic Acids Research (2007 SCI Impact = 6.954). miRNAMap was selected as hot research in 2006 NAR Database Issue. miRNAMap was genomics maps for microRNA genes and their targets in metazoan genomes (Nucl Acids Res, 2006, Nucl Acids Res, 2008). ViTa is a database of host microRNA targets on viruses (Nucl Acids Res, 2007). We also survey the literatures to extract the RNA structural motifs and their functions to construct the RegRNA database (Nucl Acids Res, 2006). The RNAMST web server was developed for searching RNA structural homologs (Nucl Acids Res, 2006). RNALogo is designed as a new approach to display structural RNA alignment (Nucl Acids Res, 2008). These databases and tools were cited more than 53 times during last two years.
[Protein Post-translational Modification: Database and Tools]
Protein Post-Translational Modification (PTM) plays an essential role in cellular control mechanisms that adjust protein physical and chemical properties, folding, conformation, stability and activity, thus also altering protein function. Four articles in this filed were published in Nucleic Acids Research (2007 SCI Impact = 6.954). dbPTM is a comprehensive information repository of protein post-translational modification (PTM) (Nucl Acids Res, 2006). Furthermore, we developed KinasePhos [1.0, 2.0], which is a web tool for identifying protein kinase-specific phosphorylation site (Nucl Acids Res, 2005, 2007, J. Comp Chem 2005). Besides, ProKware was designed as an integrated software for presenting protein structural properties in protein tertiary structures (Nucl Acids Res, 2006). These database and tools were totally cited more than 50 times during last three years.
Molecular Anticancer Lab – PI: Dr. Jui-I Chao
In recent five years, our projects focused on exploring the role and regulation of survivin in human cancer cells. My laboratory has contributed several novel findings on the roles of survivin to the academic world and further applications. Besides, we investigated potential anticancer drugs from Chinese herbs, flavonoids, and novel synthetic agents. In addition, our team has achieved some pioneering works studying nanodiamond (ND) for bio-applications. Overall, we have contributed high impact findings on survivin and nanodiamond to the academic world and further applications.
Biochemical and Genetic Engineering Lab –PI: Dr. Hsien-Tai Chiu
- Functional Genomics of Natural Products Biosynthesis from Drug-Producing Organisms
- Combinatorial Biosynthesis of Natural Products Biosynthetic Gene Clusters
- Pathway Engineering of Microorganisms for Biotransformation and Biocatalysis
- Comparative Genomics of Microbial Pathogens for Chemical Genomics
- Enzymology and Protein Engineering
a. Study of enzyme functions and catalytic mechanisms
b. Creation of novel enzymes by DNA recombination and Mutagenesis
c. Applications of biocatalyst/enzymes in novel organic transformation and drug discovery
- Stem Cells for Directed Differentiation and Proliferation
- Systems Biology and Bioinformatics
a. Networking of genomic information with expression profiles (RNA and proteomics), biosynthetic and metabolic pathways/networks (metabolomics) and functional production of useful materials (functional genomics). b. Systematic in silicon analysis.
Immunology and Oncology Lab–PI: Dr. Kuang-Wen Liao
- Immunology: Our research has indicated that the virulent molecule— Hsp60 of H. pylori was one of the major protein to inhibit the immunity of host. And we further test the effect of the Hsp60 on other tissue cells.
- Liposome: We have established the novel liposome's structure and producing procedure. Furthermore, we will deeply research the mechanism of its stably and quickly adsorptive function. Simultaneously, we will package the drug into this liposome and combine the targeting molecule to achieve specific drug delivery.
- Production of antibody and protein engineering: We have established the chimeric protein which combined a portion of VEGF and IgG Fc. Further, we used this chimeric protein to treat the tumor cell and this kind therapeutical method could efficiently inhibit the tumor growth.
Computational Chemistry Lab– PI: Dr. Jen-Shiang Yu
Theoretical coordination chemistry. Theories based on quantum mechanics are beneficial to investigate the characters of multiple bonding between transition metals as well as the reaction mechanisms. Metalloproteins can be simulated by similar approaches.
Structures and reactions of proteins. Quantum theories are widely used to study the conformational structures, reaction properties and other biological significance of proteins. Applicable methodologies include ab initio methods, density function theories, semi- empirical methods as well as molecular mechanics, and their mathematical hybrids.
Evolutionary Bioinformatics Lab – PI: Dr. Yeong-Shin Lin
Many Saccharomyces cerevisiae duplicate genes that were derived from an ancient whole-genome duplication (WGD) unexpectedly show a small synonymous divergence (K S), a higher sequence similarity to each other than to orthologues in Saccharomyces bayanus, or slow evolution compared with the orthologue in Kluyveromyces waltii, a non-WGD species. This decelerated evolution was attributed to gene conversion between duplicates. Using ≈300 WGD gene pairs in four species and their orthologues in non-WGD species, we show that codon-usage bias and protein-sequence conservation are two important causes for decelerated evolution of duplicate genes, whereas gene conversion is effective only in the presence of strong codon-usage bias or protein-sequence conservation. Furthermore, we find that change in mutation pattern or in tDNA copy number changed codon-usage bias and increased the K S distance between K. waltii and S. cerevisiae. Intriguingly, some proteins showed fast evolution before the radiation of WGD species but little or no sequence divergence between orthologues and paralogues thereafter, indicating that functional conservation after the radiation may also be responsible for decelerated evolution in duplicates.
Y.-S. Lin, J.K. Byrnes, J.-K. Hwang, and W.-H. Li*. (2006). Codon usage bias versus gene conversion in the evolution of yeast duplicate genes. Proc. Natl. Acad. Sci. USA. 103: 14412-14416.
Cognitive Neuroscience Lab – PI: Dr. Tzai-Wen Chiu
.We used the extracellular recording techiniques combined with time-frequency analysis to characterized the collicular neornal responsiveness. The picture shows the spectrotemporal receptive field of three different types of collicular neuons. (A): FM-insensitive; (B) FM specialized and (C) FM-mixed cells.
- We use the time-frequecy analysis to characterize the ECoG traces of responses to different sound stimuli from the human subjects. This work is collaborated with the Dept. Neurology, University of Iowa and the Dept. of Physiology, NCKU.
- The above picuture shows (A) ERSP responses from STG of a subject when fast and slow FM stimuli which are presented in the same 5-min session in randomorders. Increases in gamma band activity (red) are found at some channels of 96-contact grid.
Cytoskeleton and Cellular Morphogenesis Lab – PI: Dr. Eric Hwang
We used pluripotent P19 cells to study the function of microtubule-associated proteins during neuritogenesis. Multi-dimensional protein identification technology (one type of gel-free high throughput proteomics) was performed on microtubule-associated proteins prepared before versus shortly after neurite induction. More than 800 proteins were consistently identified in both proteomes. Surprisingly, when these two proteomes were quantitatively compared, the majority of the proteome remain unchanged. Substantial changes in the microtubule-associated proteome occurred at the level of individual proteins. Based on our proteomic results, we assayed primary neurons using RNA interference to identify a novel inhibitory role for protein TRIM2 in neurite elongation.