3,701 research outputs found

    Phages and human health: More than idle hitchhikers

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    Bacterial riboproteogenomics : the era of N-terminal proteoform existence revealed

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    With the rapid increase in the number of sequenced prokaryotic genomes, relying on automated gene annotation became a necessity. Multiple lines of evidence, however, suggest that current bacterial genome annotations may contain inconsistencies and are incomplete, even for so-called well-annotated genomes. We here discuss underexplored sources of protein diversity and new methodologies for high-throughput genome re-annotation. The expression of multiple molecular forms of proteins (proteoforms) from a single gene, particularly driven by alternative translation initiation, is gaining interest as a prominent contributor to bacterial protein diversity. In consequence, riboproteogenomic pipelines were proposed to comprehensively capture proteoform expression in prokaryotes by the complementary use of (positional) proteomics and the direct readout of translated genomic regions using ribosome profiling. To complement these discoveries, tailored strategies are required for the functional characterization of newly discovered bacterial proteoforms

    The physicist's guide to one of biotechnology's hottest new topics: CRISPR-Cas

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    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) constitute a multi-functional, constantly evolving immune system in bacteria and archaea cells. A heritable, molecular memory is generated of phage, plasmids, or other mobile genetic elements that attempt to attack the cell. This memory is used to recognize and interfere with subsequent invasions from the same genetic elements. This versatile prokaryotic tool has also been used to advance applications in biotechnology. Here we review a large body of CRISPR-Cas research to explore themes of evolution and selection, population dynamics, horizontal gene transfer, specific and cross-reactive interactions, cost and regulation, non-immunological CRISPR functions that boost host cell robustness, as well as applicable mechanisms for efficient and specific genetic engineering. We offer future directions that can be addressed by the physics community. Physical understanding of the CRISPR-Cas system will advance uses in biotechnology, such as developing cell lines and animal models, cell labeling and information storage, combatting antibiotic resistance, and human therapeutics.Comment: 75 pages, 15 figures, Physical Biology (2018

    White Paper 2: Origins, (Co)Evolution, Diversity & Synthesis Of Life

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    Publicado en Madrid, 185 p. ; 17 cm.How life appeared on Earth and how then it diversified into the different and currently existing forms of life are the unanswered questions that will be discussed this volume. These questions delve into the deep past of our planet, where biology intermingles with geology and chemistry, to explore the origin of life and understand its evolution, since “nothing makes sense in biology except in the light of evolution” (Dobzhansky, 1964). The eight challenges that compose this volume summarize our current knowledge and future research directions touching different aspects of the study of evolution, which can be considered a fundamental discipline of Life Science. The volume discusses recent theories on how the first molecules arouse, became organized and acquired their structure, enabling the first forms of life. It also attempts to explain how this life has changed over time, giving rise, from very similar molecular bases, to an immense biological diversity, and to understand what is the hylogenetic relationship among all the different life forms. The volume further analyzes human evolution, its relationship with the environment and its implications on human health and society. Closing the circle, the volume discusses the possibility of designing new biological machines, thus creating a cell prototype from its components and whether this knowledge can be applied to improve our ecosystem. With an effective coordination among its three main areas of knowledge, the CSIC can become an international benchmark for research in this field

    Genomics of Mycobacterium tuberculosis: old threats & new trends

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    Tuberculosis (TB) has been declared as a global health emergency by the World Health Organization (WHO). This has been mainly due to the emergence of multiple drug resistant strains and the synergy between tubercle bacilli and the human immunodeficiency virus (HIV). Genomic analysis of strains for outbreak investigations is in vogue for about a decade now. However, information available from whole genome sequencing efforts and comparative genomics of laboratory and field strains is likely to revolutionize efforts towards understanding molecular pathogenesis and dissemination dynamics of this dreaded disease. Genomic information is also going to fuel discovery projects where new targets will be identified and explored towards a new drug for TB. Besides this, efforts of information technologists, chemists, population biologists, freelance workers, media persons, non-governmental organizations and administrators to needed to handle the problem of tuberculosis to prevent it from becoming a pandemic

    Automated genome mining for natural products

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    <p>Abstract</p> <p>Background</p> <p>Discovery of new medicinal agents from natural sources has largely been an adventitious process based on screening of plant and microbial extracts combined with bioassay-guided identification and natural product structure elucidation. Increasingly rapid and more cost-effective genome sequencing technologies coupled with advanced computational power have converged to transform this trend toward a more rational and predictive pursuit.</p> <p>Results</p> <p>We have developed a rapid method of scanning genome sequences for multiple polyketide, nonribosomal peptide, and mixed combination natural products with output in a text format that can be readily converted to two and three dimensional structures using conventional software. Our open-source and web-based program can assemble various small molecules composed of twenty standard amino acids and twenty two other chain-elongation intermediates used in nonribosomal peptide systems, and four acyl-CoA extender units incorporated into polyketides by reading a hidden Markov model of DNA. This process evaluates and selects the substrate specificities along the assembly line of nonribosomal synthetases and modular polyketide synthases.</p> <p>Conclusion</p> <p>Using this approach we have predicted the structures of natural products from a diverse range of bacteria based on a limited number of signature sequences. In accelerating direct DNA to metabolomic analysis, this method bridges the interface between chemists and biologists and enables rapid scanning for compounds with potential therapeutic value.</p

    Deciphering the microbial ecology in bio- gas reactors for optimizing the anaerobic digestion process

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