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Synthetic Biology: Engineering complexity and refactoring cell capabilities

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196852 Year: Pages: 123 DOI: 10.3389/978-2-88919-685-2 Language: English
Publisher: Frontiers Media SA
Subject: Biotechnology --- General and Civil Engineering
Added to DOAB on : 2015-10-30 16:33:44
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One of the key features of biological systems is complexity, where the behavior of high level structures is more than the sum of the direct interactions between single components. Synthetic Biologists aim to use rational design to build new systems that do not already exist in nature and that exhibit useful biological functions with different levels of complexity. One such case is metabolic engineering, where, with the advent of genetic and protein engineering, by supplying cells with chemically synthesized non-natural amino acids and sugars as new building blocks, it is now becoming feasible to introduce novel physical and chemical functions and properties into biological entities. The rules of how complex behaviors arise, however, are not yet well understood. For instance, instead of considering cells as inert chassis in which synthetic devices could be easily operated to impart new functions, the presence of these systems may impact cell physiology with reported effects on transcription, translation, metabolic fitness and optimal resource allocation. The result of these changes in the chassis may be failure of the synthetic device, unexpected or reduced device behavior, or perhaps a more permissive environment in which the synthetic device is allowed to function. While new efforts have already been made to increase standardization and characterization of biological components in order to have well known parts as building blocks for the construction of more complex devices, also new strategies are emerging to better understand the biological dynamics underlying the phenomena we observe. For example, it has been shown that the features of single biological components [i.e. promoter strength, ribosome binding affinity, etc] change depending on the context where the sequences are allocated. Thus, new technical approaches have been adopted to preserve single components activity, as genomic insulation or the utilization of prediction algorithms able to take biological context into account. There have been noteworthy advances for synthetic biology in clinical technologies, biofuel production, and pharmaceuticals production; also, metabolic engineering combined with microbial selection/adaptation and fermentation processes allowed to make remarkable progress towards bio-products formation such as bioethanol, succinate, malate and, more interestingly, heterologous products or even non-natural metabolites. However, despite the many progresses, it is still clear that ad hoc trial and error predominates over purely bottom-up, rational design approaches in the synthetic biology community. In this scenario, modelling approaches are often used as a descriptive tool rather than for the prediction of complex behaviors. The initial confidence on a pure reductionist approach to the biological world has left space to a new and deeper investigation of the complexity of biological processes to gain new insights and broaden the categories of synthetic biology. In this Research Topic we host contributions that explore and address two areas of Synthetic Biology at the intersection between rational design and natural complexity: (1) the impact of synthetic devices on the host cell, or "chassis" and (2) the impact of context on the synthetic devices. Particular attention will be given to the application of these principles to the rewiring of cell metabolism in a bottom-up fashion to produce non-natural metabolites or chemicals that should eventually serve as a substitute for petrol-derived chemicals, and, on a long-term view, to provide economical, ecological and ethical solutions to today’s energetic and societal challenges.

The Emerging Discipline of Quantitative Systems Pharmacology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196425 Year: Pages: 97 DOI: 10.3389/978-2-88919-642-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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In 2011, the National Institutes of Health (NIH), in collaboration with leaders from the pharmaceutical industry and the academic community, published a white paper describing the emerging discipline of Quantitative Systems Pharmacology (QSP), and recommended the establishment of NIH-supported interdisciplinary research and training programs for QSP. QSP is still in its infancy, but has tremendous potential to change the way we approach biomedical research. QSP is really the integration of two disciplines that have been increasingly useful in biomedical research; “Systems Biology” and “Quantitative Pharmacology”. Systems Biology is the field of biomedical research that seeks to understand the relationships between genes and biologically active molecules to develop qualitative models of these systems; and Quantitative Pharmacology is the field of biomedical research that seeks to use computer aided modeling and simulation to increase our understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, and to aid in the design of pre-clinical and clinical experiments. The purpose of QSP modeling is to develop quantitative computer models of biological systems and disease processes, and the effects of drug PK and PD on those systems. QSP models allow testing of numerous potential experiments “in-silico” to eliminate those associated with a low probability of success, avoiding the potential costs of evaluating all of those failed experiments in the real world. At the same time, QSP models allow us to develop our understanding of the interaction between drugs and biological systems in a more systematic and rigorous manner. As the need to be more cost-efficient in the use of research funding increases, biomedical researchers will be required to gain the maximum insight from each experiment that is conducted. This need is even more acute in the pharmaceutical industry, where there is tremendous competition to develop innovative therapies in a highly regulated environment, combined with very high research and development (R&D) costs for bringing new drugs to market (~$1.3 billion/drug). Analogous modeling & simulation approaches have been successfully integrated into other disciplines to improve the fundamental understanding of the science and to improve the efficiency of R&D (e.g., physics, engineering, economics, etc.). The biomedical research community has been slow to integrate computer aided modeling & simulation for many reasons: including the perception that biology and pharmacology are “too complex” and “too variable” to be modeled with mathematical equations; a lack of adequate graduate training programs; and the lack of support from government agencies that fund biomedical research. However, there is an active community of researchers in the pharmaceutical industry, the academic community, and government agencies that develop QSP and quantitative systems biology models and apply them both to better characterize and predict drug pharmacology and disease processes; as well as to improve efficiency and productivity in pharmaceutical R&D.

Antimicrobial Peptides

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ISBN: 9783038420729 9783038420736 Year: Pages: 336 DOI: 10.3390/books978-3-03842-073-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-10-22 10:29:38
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Antimicrobial peptides (AMPs) are gene-encoded, ancient (and important) mediators of innate host defense that exert direct or indirect antimicrobial action as well as possessing other important biologic activities (e.g., neutralization of endotoxin and anti-biofilm action) that help to protect vertebrates, invertebrates and plants from invading pathogens. While the emergence of multi-antibiotic resistant pathogens (and the desperate need to develop new anti-infectives) has been a recent force driving the field, interest in AMPs has an earlier origin in studies of how phagocytes kill bacteria by oxygen-independent processes. AMPs responsible for such killing of microbes by rabbit and human neutrophils were later purified by Ganz, Selsted and Lehrer, which they termed defensins; at the time of this writing, literally thousands of defensin-based publications can be found in the scientific literature! The initial reports on defensins and the earlier report by Boman’s group on the purification and action of an insect AMP represented a historical and defining point for the AMP field as they, in hindsight, demanded the recognition of AMP research as a unique discipline that has important linkages to other important fields of medicine, especially those of microbiology, infectious diseases and immunology. On a personal note, I remember conferences on phagocytes and host defense in the early 1980s where the topic of AMPs was relegated to one short session in a five day period! Now, we have hundreds of international “AMPologists” with expertise in chemistry, biochemistry, molecular and structural biology, cell biology, microbiology, pharmacology, or medicine who have built their research careers around AMPs and can now attend international conferences dedicated to advances in AMP research.

Structural and computational glycobiology: immunity and infection

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196388 Year: Pages: 102 DOI: 10.3389/978-2-88919-638-8 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-10-30 16:33:44
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Interest in understanding the biological role of carbohydrates has increased significantly over the last 20 years. The use of structural techniques to understand carbohydrate-protein recognition is still a relatively young area, but one that is of emerging importance. The high flexibility of carbohydrates significantly complicates the determination of high quality structures of their complexes with proteins. Specialized techniques are often required to understand the complexity of carbohydrate recognition by proteins. In this Research Topic, we will focus on structural and computational approaches to understanding carbohydrate recognition by proteins involved in immunity and infection. Particular areas of focus include cancer immunotherapeutics, carbohydrate-lectin interactions, glycosylation and glycosyltransferases.

Dual-Use Life Science Research and Biosecurity in the 21st Century: Social, Technical, Policy, and Ethical Challenges

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195688 Year: Pages: 95 DOI: 10.3389/978-2-88919-568-8 Language: English
Publisher: Frontiers Media SA
Subject: Public Health --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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In September 2011, scientists announced new experimental findings that would not only threaten the conduct and publication of influenza research, but would have significant policy and intelligence implications. The findings presented a modified variant of the H5N1 avian influenza virus (hereafter referred to as the H5N1 virus) that was transmissible via aerosol between ferrets. These results suggested a worrisome possibility: the existence of a new airborne and highly lethal H5N1 virus that could cause a deadly global pandemic. In response, a series of international discussions on the nature of dual-use life science arose. These discussions addressed the complex social, technical, political, security, and ethical issues related to dual-use research. This Research Topic will be devoted to contributions that explore this matrix of issues from a variety of case study and international perspectives.

Garden Learning: A Study on European Botanic Gardens' Collaborative Learning Processes

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ISBN: 9781909188631 9781909188648 9781909188655 9781909188662 Year: Pages: 194 DOI: 10.5334/bas Language: English
Publisher: Ubiquity Press Grant: FP7 Ideas: European Research Council - 266616
Subject: Sociology --- Education --- Science (General) --- Sports Science
Added to DOAB on : 2016-01-16 11:01:17
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"From 2007-2013 the European 7th Framework Program Science in Society (FP7) funded a multitude of formal and informal educational institutions to join forces and engage in alternative ways to teach science—inside and outside the classroom—all over Europe. This book reports on one of these projects named INQUIRE which was developed and implemented to support 14 Botanic Gardens and Natural History Museums in 11 European countries, to establish a collaborative learning network and expand their understanding of inquiry based science teaching (IBST). Suzanne Kapelari provides insight into the complex theoretical background and practical considerations that informed the project design and which guided the consortium through a three-year process of collaborative knowledge creation. ‘Expansive Learning Theory’ is fundamental to this approach and places emphasis on communities as learners, on transformation and creation of culture, on horizontal movement and hybridization of knowledge, and on the formation of theoretical concepts.
This book is to be considered for planning and running international science education projects as well as a multifaceted theoretical underpinning of teaching. It serves as a conceptual and practical resource for formal and informal science educators and project managers.
This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 266616."

The Proceedings from Halophiles 2013, the International Congress on Halophilic Microorganisms

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195701 Year: Pages: 264 DOI: 10.3389/978-2-88919-570-1 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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The Halophiles 2013 meeting is a multidisciplinary international congress, with a strong history of regular triennial meetings since 1978. Our mission is to bring researchers from a wide diversity of investigation interests (e.g., protein and species evolution; niche adaptation, ecology, taxonomy, genomics, metagenomics, horizontal gene transfer, gene regulation; DNA replication, repair and recombination; signal transduction; community assembly and species distribution; astrobiology; biotechnological applications; adaptation to radiation, desiccation, osmotic stress) into a single forum for the integration and synthesis of ideas and data from all three domains of life, and their viruses, yet from a single environment; salt concentrations greater than seawater. This cross-section of research informs our understanding of the microbiological world in many ways. The halophilic environment is extreme, especially above 10% NaCl, restricting life solely to microbes. The microorganisms that live there are adapted to extreme conditions, and are notable for their ability to survive high doses of radiation and desiccation. Therefore, the hypersaline environment is a model system (both the abiotic, and biologic factors) for insightful understanding regarding conditions and life in the absence of plant and animals (e.g., life on the early earth, and other solar system bodies like Mars and Europa). Lower salinity conditions (e.g., 6-10% NaCl) form luxuriant microbial mats considered modern analogues of fossilized stromatolites, which are enormous microbially produced structures fashioned during the Precambrian (and still seen today in places like Shark’s Bay, Australia). Hypersaline systems are island-like habitats spread patchily across the earth’s surface, and similar to the Galapagos Islands represent unique systems excellent for studying the evolutionary pressures that shape microbial community assembly, adaptation, and speciation. The unique adaptations to this extreme environment produce valuable proteins, enzymes and other molecules capable of remediating harsh human instigated environments, and are useful for the production of biofuels, vitamins, and retinal implants, for example. This research topic is intended to capture the breadth and depth of these topics.

Phenotypic screening in the 21st century

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194698 Year: Pages: 67 DOI: 10.3389/978-2-88919-469-8 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and the suitability of target-based drug discovery as an optimal strategy for all disease states. For monogenic diseases, target-based approaches may be well-suited to the identification of novel therapies. Most diseases, however, are caused by a combination of several genetic and environmental factors and are likely to require simultaneous modulation of multiple molecular targets/pathways for successful treatment. For such diseases, reductionist approaches focusing on individual targets rather than biological networks are unlikely to succeed and new drug development strategies are required. In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and systems biology perspective. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigour. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style. This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include: • The need for systems-based approaches in drug development • Phenotypic screening strategies • Compound libraries (natural product inspired compound collections) • Target deconvolution and identification • Target agnostic lead discovery and optimization • Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modelling) • Translational aspects • Early evaluation of selectivity and safety in a target agnostic manner

"One rotten apple spoils the whole barrel": The plant hormone ethylene, the small molecule and its complexity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196234 Year: Pages: 132 DOI: 10.3389/978-2-88919-623-4 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2016-08-16 10:34:25
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The gaseous molecule ethylene (C2H4), which is small in size and simple in structure, is a plant hormone most often associated with fruit ripening yet has a diversity of effects throughout the plant life cycle. While its agricultural effects were known even in ancient Egypt, the complexity of its mode of action and the broad spectrum of its effects and potential uses in plant physiology remain important scientific challenges today. In the last few decades, the biochemical pathway of ethylene production has been uncovered, ethylene perception and signaling have been molecularly dissected, ethylene-responsive transcription factors have been identified and numerous effects of ethylene have been described, ranging from water stress, development, senescence, reproduction plant-pathogen interactions, and of course, ripening. Thus ethylene is involved in plant development, in biotic and abiotic stress, and in reproduction. There is no stage in plant life that is not affected by ethylene, modulated by a complex and fascinating molecular machinery.

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