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Search Results: 1 - 10 of 2256 matches for " Antoine Danchin "
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The bag or the spindle: the cell factory at the time of systems' biology
Antoine Danchin
Microbial Cell Factories , 2004, DOI: 10.1186/1475-2859-3-13
Abstract: At the date of October 30th, 2004 the GOLD (http://www.genomesonline.org/ webcite) site provided links to 1205 ongoing or completed genome programmes, most of which from prokaryotic organisms. More than 40,000 pages are indexed in the WWW Browser Engine Google for the keyword "cell factory". Early in 1999 the European Union launched a research programme on the cell factory (http://europa.eu.int/comm/research/rtdinf21/en/key/03.html webcite), stating that ? The concept of the "bio-product" is as old as the knowledge involved in the making of bread, beer, wine or cheese. However, recent techniques and knowledge in molecular biology and genetics mean that living cells – from bacteria to man – are now becoming real "factories". In vast fermentation vats, engineers can direct and control natural metabolism in order to produce all sorts of substances with a high added value: proteins, amino acids, alcohols, citric acid, solvents and even bio-plastics. This industrial mastery of the mechanisms of life opens up revolutionary perspectives in the development of new kinds of medicines, foodstuffs with specific nutritional properties, and biodegradable biochemical products ? [1].Taken together these pieces of information show that exploration of the potential of microbes as industrial tools is shifting from its former status of traditional biotechnology assets to new high technology devices, meant to perform highly specific tasks, with the highest possible yields and security, and genomics as the background support. We shall not here review the use of microbes in traditional production (bread, beer, cheese and wine have been invented since the origin of the Neolithic, and perhaps even earlier [2]) but, rather, see how the coupling between knowledge of bacterial genome sequences and new genomics techniques such as expression profiling and biotechnology processes have interacted recently. The numbers of works in the domain is growing exponentially (it counts certainly in the thou
Bacteria are not Lamarckian
Antoine Danchin
Quantitative Biology , 2007,
Abstract: Instructive influence of environment on heredity has been a debated topic for centuries. Darwin's identification of natural selection coupled to chance variation as the driving force for evolution, against a formal interpretation proposed by Lamarck, convinced most scientists that environment does not specifically instruct evolution in an oriented direction. This is true for multicellular organisms. In contrast, bacteria were long thought of as prone to receive oriented influences from their environment, although much was in favour of the Darwinian route (1). In this context Cairns et al. raised a passionate debate by suggesting that bacteria generate mutations oriented by the environmental conditions (2). Several independent pieces of work subsequently demonstrated that mutations overcoming specific defects arised as a consequence of cultivation on specific media (3-7). Two diametrically opposed interpretations were proposed to explain these observations : either induction of mutations instructed by the environment (e.g. by a process involving a putative reverse transcription) or selection of variants among a large set of mutant bacteria generated when stress conditions are present. The experiments presented below indicate that the Darwinian paradigm is the most plausible.
Expression profiling in reference bacteria: dreams and reality
Antoine Danchin, Agnieszka Sekowska
Genome Biology , 2000, DOI: 10.1186/gb-2000-1-4-reviews1024
Abstract: Biology has a long history of describing and classifying objects, mostly in structural terms using the techniques and language of systematics. Even genetics, which identifies gene linkage, has often studied genes as individual entities. In these earlier approaches, a cell was considered but a bag of genes and gene products: it was not usual to find biologists asking questions about the collective behavior of these genes and proteins. Because selection pressure may act on any type of organization, the study of whole-genome sequences now enables us to consider whether genomes are simply collections of genes, or whether there is indeed something more to be discovered in terms of the structure and dynamics of cells and organisms at the global level.Functional genomics has emerged as a new discipline that uses innovative technologies for genome-wide analysis supported by information technology. It depends both on experiment and on mathematical and computational methods. High-throughput experimental technologies generate large amounts of data on gene expression, protein structure and protein interactions, for example, and powerful information systems are required to analyze these data efficiently. Transcription expression profiling can be used to investigate either the transcriptome (the totality of genes transcribed) or the proteome (the totality of the proteins produced) of a bacterium. DNA arrays and two-dimensional gel electrophoresis are expected to provide a global, high-throughput approach to revealing which genes are expressed at a detectable level, where they are expressed, and which are over- or under-expressed at a given growth stage or following changes in environmental conditions. The use of different growth conditions, different RNA extraction procedures and different array systems has created problems in comparing results, and highlights the need for benchmarking between different laboratories. Here, we review some recent articles describing expression prof
Genomes are covered with ubiquitous 11 bp periodic patterns, the "class A flexible patterns"
Etienne Larsabal, Antoine Danchin
BMC Bioinformatics , 2005, DOI: 10.1186/1471-2105-6-206
Abstract: Using a technique for analysis of auto-correlations based on linear projection, we identified the sequences responsible for the bias. Prokaryotic and lower eukaryotic genomes are covered with ubiquitous patterns that we termed "class A flexible patterns". Each pattern is composed of up to ten conserved nucleotides or dinucleotides distributed into a discontinuous motif. Each occurrence spans a region up to 50 bp in length. They belong to what we named the "flexible pattern" type, in that there is some limited fluctuation in the distances between the nucleotides composing each occurrence of a given pattern. When taken together, these patterns cover up to half of the genome in the majority of prokaryotes. They generate the previously recognized 11 bp periodic bias.Judging from the structure of the patterns, we suggest that they may define a dense network of protein interaction sites in chromosomes.The distribution of nucleotides in genomes is not random, various biases are affecting the genome sequences from organisms spanning the three domains of life. For example, the G+C content affects the genome as a whole.To visualize the biases in the nucleotides distribution in genomes, investigators have performed a variety of statistical analyses; these operations basically consisted in counting the nucleotides in a variety of subtle ways, while attempting to identify how the counting observed in real examples differed from a random distribution. Relevant statistical methods developed so far include the following: computation of correlations [1], power spectrum analysis [2,3], DNA walking analysis [4], computation of entropy [5,6], Hurst index estimation [7], detrended fluctuation analysis [8], wavelet analysis [9], mutual information function analysis [10], computational linguistics analysis [11].Among the different biases observed in the nucleotides distribution in genomes, two stood out prominently. Both are short-range biases, i.e. correlating nucleotides over a short di
The methionine salvage pathway in Bacillus subtilis
Agnieszka Sekowska, Antoine Danchin
BMC Microbiology , 2002, DOI: 10.1186/1471-2180-2-8
Abstract: Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere) as a major step in MTR recycling.A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane).The fate of methylthioribose (MTR), the end-product of spermidine and spermine metabolism, as well as of ethylene biosynthesis has not yet been fully explored in most organisms. In Escherichia coli this molecule is excreted in the medium [1] while in Klebsiella pneumoniae it constitutes the methionine salvage pathway, being metabolized back into methionine [2,3]. In eukaryotic parasites it is also recycled into methionine, presumably through a pathway similar to that in K. pneumoniae[4]. In Bacillus subtilis we found that MTR is an excellent sulfur source [5] and we unraveled some of the steps involved in its metabolism, which starts from phosphorylation of MTR, mediated by the MtnK protein [6].It has been
Antifragility and Tinkering in Biology (and in Business) Flexibility Provides an Efficient Epigenetic Way to Manage Risk
Antoine Danchin,Philippe M. Binder,Stanislas Noria
Genes , 2011, DOI: 10.3390/genes2040998
Abstract: The notion of antifragility, an attribute of systems that makes them thrive under variable conditions, has recently been proposed by Nassim Taleb in a business context. This idea requires the ability of such systems to ‘tinker’, i.e., to creatively respond to changes in their environment. A fairly obvious example of this is natural selection-driven evolution. In this ubiquitous process, an original entity, challenged by an ever-changing environment, creates variants that evolve into novel entities. Analyzing functions that are essential during stationary-state life yield examples of entities that may be antifragile. One such example is proteins with flexible regions that can undergo functional alteration of their side residues or backbone and thus implement the tinkering that leads to antifragility. This in-built property of the cell chassis must be taken into account when considering construction of cell factories driven by engineering principles.
Persistence drives gene clustering in bacterial genomes
Gang Fang, Eduardo PC Rocha, Antoine Danchin
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-4
Abstract: We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters.We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.Made of DNA, a complex chemical substrate duplicated using a complex machinery, and submitted to all kinds of chemical aggressions and accidents, bacterial genome sequences are subject to many processes leading to sequence alteration, such as point mutations, rearrangements, gene duplications, gene deletions, lateral transfer of genes, etc. [1]. The availability of a rapidly increasing number of completely sequenced bacterial genomes makes it possible to explore gene order conservation in related and distant species. Gene order is preserved extensively in closely related species, but fades away in distantly related organisms [2,3]. Comparing different species, the conservation of gene order varies in parallel with the nature of the different selection pressures imposed upon genome stability [4]. Most studies of genome rearrangements have shown a marked preference for highl
A double epidemic model for the SARS propagation
Tuen Ng, Gabriel Turinici, Antoine Danchin
BMC Infectious Diseases , 2003, DOI: 10.1186/1471-2334-3-19
Abstract: In this report, we show first that the standard Susceptible-Infected-Removed (SIR) model cannot account for the patterns observed in various regions where the disease spread. We develop a model involving two superimposed epidemics to study the recent spread of the SARS in Hong Kong and in the region. We explore the situation where these epidemics may be caused either by a virus and one or several mutants that changed its tropism, or by two unrelated viruses. This has important consequences for the future: the innocuous epidemic might still be there and generate, from time to time, variants that would have properties similar to those of SARS.We find that, in order to reconcile the existing data and the spread of the disease, it is convenient to suggest that a first milder outbreak protected against the SARS. Regions that had not seen the first epidemic, or that were affected simultaneously with the SARS suffered much more, with a very high percentage of persons affected. We also find regions where the data appear to be inconsistent, suggesting that they are incomplete or do not reflect an appropriate identification of SARS patients. Finally, we could, within the framework of the model, fix limits to the future development of the epidemic, allowing us to identify landmarks that may be useful to set up a monitoring system to follow the evolution of the epidemic. The model also suggests that there might exist a SARS precursor in a large reservoir, prompting for implementation of precautionary measures when the weather cools down.Since November 2002 (and perhaps earlier) an outbreak of a very contagious atypical pneumonia (now named Severe Acute Respiratory Syndrome) initiated in the Guangdong Province of China. This outbreak started a world-wide epidemic after a medical doctor from Guangzhou infected several persons at an hotel in Kowloon around February 21st, 2003 (SAR Hong Kong, China). Although apparently classical in its onset, the pattern of the outbreak became puz
Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli
Evelyne Krin, Antoine Danchin, Olga Soutourina
BMC Microbiology , 2010, DOI: 10.1186/1471-2180-10-273
Abstract: We combined mutational, phenotypic and gene expression analyses, to unravel the regulatory hierarchy in acid resistance involving H-NS, RcsB-P/GadE complex, HdfR, CadC, AdiY regulators, and DNA-binding assays to separate direct effects from indirect ones. RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade. However, H-NS also directly controls specific regulators of these pathways (e.g. cadC) and genes involved in general stress resistance (hdeAB, hdeD, dps, adiY). Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility.H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways.In Escherichia coli, complex cellular responses are controlled by networks of transcriptional factors that regulate the expression of a diverse set of target genes, at various hierarchical levels. H-NS, a nucleoid-associated protein, is a top level regulator affecting the expression of at least 250 genes, mainly related to the bacterial response to environmental changes [1]. Among its various targets, it regulates in opposite directions the flagella-dependent motility and the acid stress resistance [1]; the first via the control of flhDC master flagellar operon by acting both directly and indirectly via regulators HdfR and RcsB [2-6]; the second by repressing the genes involved in three amino acid decarboxylase systems, dependent on glutamate, lysine and arginine, via the RcsB-P/GadE regulatory complex [6]. In this regulatory process H-NS represses the expression of gadE (encoding the central activator of the glutamate-dependent acid resistance pathway) both in a direct and an indirect way, via EvgA, YdeO, GadX and GadW [1
Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling
Yee Yap, Xue Zhang, Antoine Danchin
BMC Bioinformatics , 2003, DOI: 10.1186/1471-2105-4-43
Abstract: Both approaches yielded relationship outcomes that are consistent with the known virus classification. They also indicated that the genome of RNA viruses from the same family conform to a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usage patterns, the Transmissible Gastroenteritis Virus (TGV) and the Feline CoronaVirus (FCoV) are closest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stage displayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48 respectively) and selection for UpG and CpA (z = 65.79,49.99 respectively). Potential factors influencing these biases are discussed.The study of genomic word usage is a powerful method to classify RNA viruses. The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames.Severe Acute Respiratory Syndrome (SARS), a newly identified infectious disease, has imperilled the health of human population in more than 30 nations. It has claimed over 812 lives and infected more than 8442 (9.61% death rate) by July 2, 2003 [1] since its outbreak in November 2002 in the province of GuangDong, People's Republic of China. By May 15, 2003, the primary etiological agent for SARS was found to fulfil Koch's postulate through experimental infection of cynomolgus macaques (Macaca fascicularis) [2]. Chronicles for the discovery of SARS CoronaVirus (SARS-CoV) can be found in articles [e.g. [3,4]] and websites [e.g. [5]].A common question is often asked when investigating viral evolution: what hallmark, in term of genome sequence or RNA word usage, could be used to trace back the emergence of a new pathogen in humans/animals? In particular, CoronaViruses are prone to recombination [6,7] and like all other viruses they mutate at a high frequency [8]. This makes extremely hazardou
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