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Systems Biology and the Challenge of Deciphering the Metabolic Mechanisms Underlying Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453337 Year: Pages: 142 DOI: 10.3389/978-2-88945-333-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology --- Biology
Added to DOAB on : 2018-11-16 17:17:57
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Since the discovery of the Warburg effect in the 1920s cancer has been tightly associated with the genetic and metabolic state of the cell. One of the hallmarks of cancer is the alteration of the cellular metabolism in order to promote proliferation and undermine cellular defense mechanisms such as apoptosis or detection by the immune system. However, the strategies by which this is achieved in different cancers and sometimes even in different patients of the same cancer is very heterogeneous, which hinders the design of general treatment options.Recently, there has been an ongoing effort to study this phenomenon on a genomic scale in order to understand the causality underlying the disease. Hence, current “omics” technologies have contributed to identify and monitor different biological pieces at different biological levels, such as genes, proteins or metabolites. These technological capacities have provided us with vast amounts of clinical data where a single patient may often give rise to various tissue samples, each of them being characterized in detail by genomescale data on the sequence, expression, proteome and metabolome level. Data with such detail poses the imminent problem of extracting meaningful interpretations and translating them into specific treatment options. To this purpose, Systems Biology provides a set of promising computational tools in order to decipher the mechanisms driving a healthy cell’s metabolism into a cancerous one. However, this enterprise requires bridging the gap between large data resources, mathematical analysis and modeling specifically designed to work with the available data. This is by no means trivial and requires high levels of communication and adaptation between the experimental and theoretical side of research.

Quantitative Systems Biology for Engineering Organisms and Pathways

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198290 Year: Pages: 126 DOI: 10.3389/978-2-88919-829-0 Language: English
Publisher: Frontiers Media SA
Subject: Biotechnology --- General and Civil Engineering
Added to DOAB on : 2016-01-19 14:05:46
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Studying organisms as a whole for potential metabolic(ally) engineering of organisms for production of (bio)chemicals is essential for industrial biotechnology. To this end, integrative analysis of different –omics measurements (transciptomics, proteomics, metabolomics, fluxomics) provides invaluable information. Combination of experimental top-down and bottom-up approaches with powerful analytical tools/techniques and mathematical modeling, namely (quantitative) systems biology, currently making the state of art of this discipline, is the only practice that would improve our understanding for the purpose. The use of high-throughput technologies induced the required development of many bioinformatics tools and mathematical methods for the integration of obtained data. Such research is significant since compiling information from different levels of a living system and connecting them is not an easy task. In particular, construction of dynamic models for product improvement has been one of the goals of many research groups. In this Research Topic, we summarize and bring a general review of the most recent and relevant contributions in quantitative systems biology applied in metabolic modeling perspective. We want to make special emphasis on the techniques that can be widely implemented in regular scientific laboratories and in those works that include theoretical presentations. With this Research Topic we discuss the importance of applying systems biology approaches for finding metabolic engineering targets for the efficient production of the desired biochemical integrating information from genomes and networks to industrial production. Examples and perspectives in the design of new industrially relevant chemicals, e.g. increased titer/productivity/yield of (bio)chemicals, are welcome. Addition to the founded examples, potential new techniques that would frontier the research will be part of this topic. The significance of multi ‘omics’ approaches to understand/uncover the pathogenesis/mechanisms of metabolic diseases is also one of the main topics.

Metal Biology Takes Flight: The Study of Metal Homeostasis and Detoxification in Insects

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455560 Year: Pages: 144 DOI: 10.3389/978-2-88945-556-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics --- Physiology
Added to DOAB on : 2019-01-23 14:53:42
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Metals such as copper, iron, manganese, and zinc are clearly required for proper metabolism and development, while imbalances can lead to systemic dysfunction and disease. As a result, organisms have evolved complex genetic systems for the regulation of metal levels, including import, export, and sequestration of metals within cells and sub-cellular compartments.

The study of metal biology in insects has the potential to greatly expand our understanding of metal biology. The results of such studies might point to new possible therapeutic interventions for neurological and other human diseases, as well as new strategies for insect disease vector control.

The articles collected in this Research Topic comprise review and original research on metal biology in insects.

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.

Protein Phosphorylation in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199006 Year: Pages: 122 DOI: 10.3389/978-2-88919-900-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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Protein phosphorylation is one of the most abundant reversible post-translational modifications in eukaryotes. It is involved in virtually all cellular processes by regulating protein function, localization and stability and by mediating protein-protein interactions. Furthermore, aberrant protein phosphorylation is implicated in the onset and progression of human diseases such as cancer and neurodegenerative disorders. In the last years, tens of thousands of in vivo phosphorylation events have been identified by large-scale quantitative phospho-proteomics experiment suggesting that a large fraction of the proteome might be regulated by phosphorylation. This data explosion is increasingly enabling the development of computational approaches, often combined with experimental validation, aiming at prioritizing phosphosites and assessing their functional relevance. Some computational approaches also address the inference of specificity determinants of protein kinases/phosphatases and the identification of phosphoresidue recognition domains. In this context, several challenging issues are still open regarding phosphorylation, including a better understanding of the interplay between phosphorylation and allosteric regulation, agents and mechanisms disrupting or promoting abnormal phosphorylation in diseases, the identification and modulation of novel phosphorylation inhibitors, and so forth. Furthermore, the determinants of kinase and phosphatase recognition and binding specificity are still unknown in several cases, as well as the impact of disease mutations on phosphorylation-mediated signaling. The articles included in this Research Topic illustrate the very diverse aspects of phosphorylation, ranging from structural changes induced by phosphorylation to the peculiarities of phosphosite evolution. Some also provide a glimpse into the huge complexity of phosphorylation networks and pathways in health and disease, and underscore that a deeper knowledge of such processes is essential to identify disease biomarkers, on one hand, and design more effective therapeutic strategies, on the other.

Advances in Systems Immunology and Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193134 Year: Pages: 108 DOI: 10.3389/978-2-88919-313-4 Language: English
Publisher: Frontiers Media SA
Subject: Genetics --- Biology --- Biotechnology --- General and Civil Engineering --- Psychiatry --- Medicine (General) --- Physiology --- Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Aims and Scope: The Research Topic is designed to feature the latest innovative and leading-edge research, reviews and opinions on the study of complex and dynamic processes related to the mammalian immune system and cancer. All papers were meticulously selected to present our readers the multidisciplinary approach to tackle the existing challenges faced in these important fields. From high throughput experimental methodologies to computational and theoretical approaches, the articles are intended to introduce physicists, chemists, computer scientists, biologists and immunologists the idea of systems biology approach to the understanding of mammalian immune system and cancer processes. Attention was given to works that developed more effective approaches to the treatment of proinflammatory disease and cancer. The strong interdisciplinary focus will discuss biological systems at the level from a few molecules to the entire organism. Specific focus domain includes: Innate and adaptive immunity, cancer and cancer stem cell, genomic, proteomic and metabolic analysis, imaging, biophysics of immune and cancer response, computational modeling, non-linear analysis, statistical analysis, translational and disease models Types of articles: Viewpoint, commentaries, research letters, research articles, review and methodologies

Salinity Tolerance in Plants: Mechanisms and Regulation of Ion Transport

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453696 Year: Pages: 243 DOI: 10.3389/978-2-88945-369-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2018-02-27 16:16:45
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Life presumably arose in the primeval oceans with similar or even greater salinity than the present ocean, so the ancient cells were designed to withstand salinity. However, the immediate ancestors of land plants most likely lived in fresh, or slightly brackish, water. The fresh/brackish water origins might explain why many land plants, including some cereals, can withstand moderate salinity, but only 1 – 2 % of all the higher plant species were able to re-discover their saline origins again and survive at increased salinities close to that of seawater. From a practical side, salinity is among the major threats to agriculture, having been one of the reasons for the demise of the ancient Mesopotamian Sumer civilisation and in the present time causing huge annual economic losses of over 10 billion USD. The effects of salinity on plants include osmotic stress, disruption of membrane ion transport, direct toxicity of high cytoplasmic concentrations of sodium and chloride on cellular processes and induced oxidative stress. Ion transport is the crucial starting point that determines salinity tolerance in plants. Transport via membranes is mediated mostly by the ion channels and transporters, which ensure selective passage of specific ions. The molecular and structural diversity of these ion channels and transporters is amazing. Obtaining the detailed descriptions of distinct ion channels and transporters present in halophytes, marine algae and salt-tolerant fungi and then progressing to the cellular and the whole organism mechanisms, is one of the logical ways to understand high salinity tolerance. Transfer of the genes from halophytes to agricultural crops is a means to increase salt tolerance of the crops. The theoretical scientific approaches involve protein chemistry, structure-function relations of membrane proteins, synthetic biology, systems biology and physiology of stress and ion homeostasis. At the time of compiling this e-book many aspects of ion transport under salinity stress are not yet well understood. The e-book has attracted researchers in ion transport and salinity tolerance. We have combined our efforts to achieve a wider, more detailed understanding of salt tolerance in plants mediated by ion transport, to understand present and future ways to modify and manipulate ion transport and salinity tolerance and also to find natural limits for the modifications.

Foundations of Theoretical Approaches in Systems Biology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456833 Year: Pages: 216 DOI: 10.3389/978-2-88945-683-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2019-01-23 14:53:43
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If biology in the 20th century was characterized by an explosion of new technologies and experimental methods, that of the 21st has seen an equally exuberant proliferation of mathematical and computational methods that attempt to systematize and explain the abundance of available data. As we live through the consolidation of a new paradigm where experimental data goes hand in hand with computational analysis, we contemplate the challenge of fusing these two aspects of the new biology into a consistent theoretical framework. Whether systems biology will survive as a field or be washed away by the tides of future fads will ultimately depend on its success to achieve this type of synthesis. The famous quote attributed to Kurt Lewin comes to mind: "there is nothing more practical than a good theory". This book presents a wide assortment of articles on systems biology in an attempt to capture the variety of current methods in systems biology and show how they can help to find answers to the challenges of modern biology.

Precision Medicine in Oncology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457052 Year: Pages: 163 DOI: 10.3389/978-2-88945-705-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2019-01-23 14:53:43
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The emerging precision medicine approach aims to tailor disease prevention and treatment to each patient on the basis of individual variability, environmental factors and lifestyle. Fundamental achievements in the last few decades have converged to offer nowadays the compelling opportunity to move towards this innovative approach: i) unprecedented improvements in disease modeling in silico, in vitro and in vivo; ii) acquisition of a wide range of biomedical information combined with the development of computational toolsets for flexible and integrative analyses of multi-assay datasets. Our deeper understanding of oncogenic mechanisms has finally begun to have a crucial impact on clinical decisions at several steps, from cancer prevention and diagnosis to therapeutic intervention. However, precision oncology still encounters several unresolved hurdles including tumour heterogeneity and recurrence as well as unexplained drug resistance and lack of effective ways to monitor response to therapeutic treatments. Notably, limitations in biomedical research regulation and governance represent additional debatable issues that need careful consideration.

Biological Ontologies and Semantic Biology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192779 Year: Pages: 106 DOI: 10.3389/978-2-88919-277-9 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Biotechnology --- General and Civil Engineering --- Genetics --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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As the amount of biological information and its diversity accumulates massively there is a critical need to facilitate the integration of this data to allow new and unexpected conclusions to be drawn from it. The Semantic Web is a new wave of web- based technologies that allows the linking of data between diverse data sets via standardised data formats (“big data”). Semantic Biology is the application of semantic web technology in the biological domain (including medical and health informatics). The Special Topic encompasses papers in this very broad area, including not only ontologies (development and applications), but also text mining, data integration and data analysis making use of the technologies of the Semantic Web. Ontologies are a critical requirement for such integration as they allow conclusions drawn about biological experiments, or descriptions of biological entities, to be understandable and integratable despite being contained in different databases and analysed by different software systems. Ontologies are the standard structures used in biology, and more broadly in computer science, to hold standardized terminologies for particular domains of knowledge. Ontologies consist of sets of standard terms, which are defined and may have synonyms for ease of searching and to accommodate different usages by different communities. These terms are linked by standard relationships, such as “is_a” (an eye “is_a” sense organ) or “part_of” (an eye is “part_of” a head). By linking terms in this way, more detailed, or granular, terms can be linked to broader terms, allowing computation to be carried out that takes these relationships into account.

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