• Title/Summary/Keyword: gene discovery

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Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Daniel M. Miller
    • Korean Journal of Microbiology
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    • v.38 no.4
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    • pp.203-203
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    • 2002
  • Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

Applied Computational Tools for Crop Genome Research

  • Love Christopher G;Batley Jacqueline;Edwards David
    • Journal of Plant Biotechnology
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    • v.5 no.4
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    • pp.193-195
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    • 2003
  • A major goal of agricultural biotechnology is the discovery of genes or genetic loci which are associated with characteristics beneficial to crop production. This knowledge of genetic loci may then be applied to improve crop breeding. Agriculturally important genes may also benefit crop production through transgenic technologies. Recent years have seen an application of high throughput technologies to agricultural biotechnology leading to the production of large amounts of genomic data. The challenge today is the effective structuring of this data to permit researchers to search, filter and importantly, make robust associations within a wide variety of datasets. At the Plant Biotechnology Centre, Primary Industries Research Victoria in Melbourne, Australia, we have developed a series of tools and computational pipelines to assist in the processing and structuring of genomic data to aid its application to agricultural biotechnology resear-ch. These tools include a sequence database, ASTRA, for the processing and annotation of expressed sequence tag data. Tools have also been developed for the discovery of simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) molecular markers from large sequence datasets. Application of these tools to Brassica research has assisted in the production of genetic and comparative physical maps as well as candidate gene discovery for a range of agronomically important traits.

Screening of New Antibiotics Inhibiting Bacterial Peptide Deformylase (PDF) (세균의 Peptide Deformylase(PDF)를 억제하는 새로운 항균물질의 스크리닝)

  • 곽진환;김현주;설민정;서병선;이종국;최수영
    • YAKHAK HOEJI
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    • v.47 no.3
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    • pp.184-189
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    • 2003
  • Peptide deformylase (PDF) is essential and unique to bacteria, thus making it an attractive target for the discovery of novel antibacterial drugs. PDF deformylates the N-formylmethionine of newly synthesized polypeptides in prokaryotes. In this study, a pdf gene from Staphylococcus aureus 6538p was cloned in pET-14b vector and PDF protein was over-produced in Escherichia coli BL21 (DE3). NH$_2$-terminal His-tagged PDF protein was purified by nickel-nitrilotriacetic acid (Ni-NTA) metal-affinity chromatography. Enzymatic activity of purified 6xHis-tagged PDF was tested on the substrate (formyl-Methionine-Alanine-Serine) by formate dehydrogenase-coupled spectrometric assay of peptide deformylase. For the discovery of new PDF inhibitors from chemical libraries and culture broths of soil bacteria, a target-oriented screening system using a 96-well plate was developed. About 3,000 commercial chemical libraries were tested in this screening system, and 2 chemicals (0.07%) among them showed an inhibitory activity against PDF enzyme. This result showed that a new screening system can be used for the discovery of new PDF inhibitors.

Identification of Differentially Expressed Genes by cDNA-AFLP in Magnaporthe oryzae

  • Chi, Myoung-Hwan;Park, Sook-Young
    • Research in Plant Disease
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    • v.25 no.4
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    • pp.205-212
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    • 2019
  • Analysis of differentially expressed genes has assisted discovery of gene sets involved in particular biological processes. The purpose of this study was to identify genes involved in appressorium formation in the rice blast fungus Magnaporthe oryzae via analysis of cDNA-amplified fragment length polymorphisms. Amplification of appressorial and vegetative mycelial cDNAs using 28 primer combinations generated over 200 differentially expressed transcript-derived fragments (TDFs). TDFs were excised from gels, re-amplified by PCR, cloned, and sequenced. Forty-four of 52 clones analyzed corresponded to 42 genes. Quantitative real-time PCR showed that expression of 23 genes was up-regulated during appressorium formation, one of which was the MCK1 gene that had been shown to be involved in appressorium formation. This study will be providing valuable resources for identifying the genes such as pathogenicity-related genes in M. oryzae.

One-Step Selection of Artificial Transcription Factors Using an In Vivo Screening System

  • Bae, Kwang-Hee;Kim, Jin-Soo
    • Molecules and Cells
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    • v.21 no.3
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    • pp.376-380
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    • 2006
  • Gene expression is regulated in large part at the level of transcription under the control of sequence-specific transcriptional regulatory proteins. Therefore, the ability to affect gene expression at will using sequencespecific artificial transcription factors would provide researchers with a powerful tool for biotechnology research and drug discovery. Previously, we isolated 56 novel sequence-specific DNA-binding domains from the human genome by in vivo selection. We hypothesized that these domains might be more useful for regulating gene expression in higher eukaryotic cells than those selected in vitro using phage display. However, an unpredictable factor, termed the "context effect", is associated with the construction of novel zinc finger transcription factors--- DNA-binding proteins that bind specifically to 9-base pair target sequences. In this study, we directly selected active artificial zinc finger proteins from a zinc finger protein library. Direct in vivo selection of constituents of a zinc finger protein library may be an efficient method for isolating multi-finger DNA binding proteins while avoiding the context effect.

Understanding the genetics of systemic lupus erythematosus using Bayesian statistics and gene network analysis

  • Nam, Seoung Wan;Lee, Kwang Seob;Yang, Jae Won;Ko, Younhee;Eisenhut, Michael;Lee, Keum Hwa;Shin, Jae Il;Kronbichler, Andreas
    • Clinical and Experimental Pediatrics
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    • v.64 no.5
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    • pp.208-222
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    • 2021
  • The publication of genetic epidemiology meta-analyses has increased rapidly, but it has been suggested that many of the statistically significant results are false positive. In addition, most such meta-analyses have been redundant, duplicate, and erroneous, leading to research waste. In addition, since most claimed candidate gene associations were false-positives, correctly interpreting the published results is important. In this review, we emphasize the importance of interpreting the results of genetic epidemiology meta-analyses using Bayesian statistics and gene network analysis, which could be applied in other diseases.

Screening of New Antibiotics Inhibiting Bacterial Enoyl-Acyl Carrier Protein Reductase (Fabl) (세균의 지방산 생합성 효소 (Enoyl-Acyl Carrier Protein Reductase, FabI)를 저해하는 새로운 항균물질의 스크리닝)

  • 곽진환
    • YAKHAK HOEJI
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    • v.46 no.1
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    • pp.24-29
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    • 2002
  • Enoyl-Acyl Carrier Protein Reductase (Fabl) of bacteria is hem as an important target for new antibacterial drugs and plays a determinant role in completing cycles of elongation in type-H fatty acid synthase system. In this study, a fabI gene from Staphylococcus aureus 6538p cloned in pET-l4b vector and FabI protein was over-produced in Escherichaia coli BL2l (DE3). $NH_2$-terminal His-tagged FabI protein was purified by nickel-nitrilotriacetic acid (Ni-NTA) metalaffinity chromatography Purified 6xHis-tagged FabI showed a catalytic activity on tram - 2 - octenoyl - N -acethlcysteamine by utilizing NADPH as a cofactor. For the discovery of new FabI inhibitors from chemical libraries, a target-oriented screening system using a 96-well plate was developed. About 10,000 chemical libraries from Korea Chemical Bank wore tested in this screening system, and 26 chemicals (0.25%) among them showed an inhibitory activity against FabI enzyme. This result showed that a new screening system can be used for the discovery of new FabI inhibitors.

Estimation of Gini-Simpson index for SNP data

  • Kang, Joonsung
    • Journal of the Korean Data and Information Science Society
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    • v.28 no.6
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    • pp.1557-1564
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    • 2017
  • We take genomic sequences of high-dimensional low sample size (HDLSS) without ordering of response categories into account. When constructing an appropriate test statistics in this model, the classical multivariate analysis of variance (MANOVA) approach might not be useful owing to very large number of parameters and very small sample size. For these reasons, we present a pseudo marginal model based upon the Gini-Simpson index estimated via Bayesian approach. In view of small sample size, we consider the permutation distribution by every possible n! (equally likely) permutation of the joined sample observations across G groups of (sizes $n_1,{\ldots}n_G$). We simulate data and apply false discovery rate (FDR) and positive false discovery rate (pFDR) with associated proposed test statistics to the data. And we also analyze real SARS data and compute FDR and pFDR. FDR and pFDR procedure along with the associated test statistics for each gene control the FDR and pFDR respectively at any level ${\alpha}$ for the set of p-values by using the exact conditional permutation theory.

DNA chip technology

  • Lee, Sang-Yeop;Yun, Seong-Ho;Choe, Jong-Gil;Im, Geun-Bae
    • 한국생물공학회:학술대회논문집
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    • 2000.11a
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    • pp.119-122
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    • 2000
  • Biological science is being revolutionized by the availability of much sequence information from many genome project With the advanced technology at hand, main trend in biological research is rapidly changing from a structural DNA analysis to understanding cellular function of the DNA sequences. Combined with mechanics, computer, bioinformatics and other advanced technologies, DNA chip technology provides numerous applications because of its robustness, accuracy, and automation. DNA chip is expected to become an indispensable tool in fields of biology, biotechnology, drug discovery, and other application areas. DNA chip can be used for mutation and polymorphism detection, gene expression monitoring and phenotypic analysis as well. If DNA chip is used for the development of pharmaceutical products, it can considerably reduce the cost and time for the entire process of drug discovery and development, and can also contribute in developing personal drugs.

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Data Mining Techniques for Medical Informatics: Application to SNP Analysis

  • Chun, Se-Hak;Kim, Jin;Park, Yoon-Joo;Ham, Ki-Baek;Chun, Se-Chul
    • Proceedings of the Korea Inteligent Information System Society Conference
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    • 2005.11a
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    • pp.258-263
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    • 2005
  • Haplotype-based analysis using high-density SNP markers have gained a great attention in evaluating genes in gene analysis and various clinical situations. However, there has been no research on disease diagnostic modeling based on SNPs analysis to our knowledge. The purpose of this study is to explore how knowledge discovery techniques are applied in medical informatics area and proposes a Case Based Reasoning (CBR) technique for diagnosis of gastric caner using Single Nucleotide Polymorphism(SNP).

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