Chemical Tools To Perturb And Observe Complex Biology
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Chemical Tools To Perturb And Observe Complex Biology
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Author : Mark Anthony Sellmyer
language : en
Publisher:
Release Date : 2010
Chemical Tools To Perturb And Observe Complex Biology written by Mark Anthony Sellmyer and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
A detailed understanding of living systems requires tools to examine and manipulate biological processes. Small molecules and optical imaging technologies are uniquely suited for this purpose. Small molecules enable the specific manipulation of biomolecular targets, and optical imaging permits the real-time observation of molecular and cellular processes in vivo. This dissertation describes a combination of chemical tool development and imaging strategies to address the following biological problems: 1) specific modification of the genome 2) exquisite control of protein function 3) observing cell-cell interactions in living animals. Chapter One describes a technology for targeted gene modification via the induction of double strand breaks in genomic DNA. The chapter begins with an overview of the field of gene targeting, and documents the design, synthesis, and testing of a novel method for high efficiency homologous recombination. The method relies on engineering two reagents, a small molecule DNA targeting element and a nuclease fusion protein. The targeting element, a peptide nucleic acid (PNA), was designed and synthesized to target DNA via Watson-Crick base pairing. The PNA also was covalently linked to the small molecule, trimethoprim, to recruit a DHFR nuclease fusion protein to a specific DNA site. Our studies show that the individual interactions of PNA/DNA and of PNA/nuclease can readily occur. Further, the ternary complex of PNA, DNA, and nuclease can form in solution. Chapters Two, Three, and Four describe the development and further characterization of a general method to perturb protein stability and function. Briefly, an unstable protein domain, termed a destabilizing domain (DD), can confer instability to a fused protein of interest and promote its rapid degradation. This instability can be rescued by the addition of a small molecule, Shield-1. Our work in Chapter Two describes the use of this system to regulate protein function in living mammals. In one example, we show that regulation of a secreted protein, the immunomodulatory cytokine IL-2, can control tumor burden in mouse models. Additionally, we used the DD to control the function of TNF-[Alpha] after systemic delivery to a tumor. Chapter Three expands on these in vivo efforts by employing the system to regulate secreted FGF2, an important modulator of bone formation, for skeletal tissue engineering. Shield-1 induction of FGF2 causes induction of bone formation in a calvarial-defect model. Chapter Four presents our observations on the behavior of the DD in various cellular environments --the cytoplasm, nucleus, endoplasmic reticulum, and mitochondria- and in the presence of small molecules that modulate protein production, degradation, and local protein quality control machinery. These data indicate that the levels of the DD, in the presence and absence ligand, is dependent on its subcellular locale and protein homeostasis machinery. The fifth chapter of this dissertation reports the development of a method to assess spatiotemporal cell-cell relationships in real-time and in living animals. The method is based on small-molecule diffusion of an activatable substrate between two populations of cells, thus allowing assessment of cell-cell proximity in vivo via bioluminescence imaging. One cell population catalyzes the release of a caged luciferin. The free luciferin can diffuse to a nearby population of cells expressing luciferase capable of light-emitting catalysis. Thus the luciferase cells in closest proximity to the "pool" of free luciferin emit the most light. We demonstrate the utility of this system in vitro and in vivo and are currently investigating its use for the detection of cancer and early metastatic disease in mouse models.
Novel Chemical Tools To Study Ion Channel Biology
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Author : Christopher Ahern
language : en
Publisher: Springer
Release Date : 2015-09-17
Novel Chemical Tools To Study Ion Channel Biology written by Christopher Ahern and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-09-17 with Medical categories.
This volume describes chemical approaches to assess ion channel structure, function and pharmacology. Topics discussed include the use of engineered ionizable side chains to obtain information on permeation pathways and the local environment; the modification of engineered cysteine side chains, including cysteine scanning mutagenesis and the attachment of fluorescent probes and bio-reactive tethers; and the nascent use of genetic code expansion, evaluating its applications to ion channel and membrane proteins. This comprehensive text provides multifaceted perspectives on the great diversity of state-of-the-art methods which take advantage of the ever-expanding chemical toolbox to study ion channel biology. Capturing the contributions and innovations of renowned laboratory researchers in transmembrane protein study for the first time, this book is comprehensive in scope. It covers a wide array of experimental approaches: photochemistry, novel biological tools, and innovative spectroscopy, all combined with traditional techniques of electrophysiology and molecular biology. Novel Chemical Tools to Study Ion Channel Biology, part of the bestselling Advances in Experimental Medicine and Biology series is ideal for researchers and advanced students interested in biochemistry, biophysics, fluorometry, electrophysiology, and chemical biology. .
Advanced Chemical Biology
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Author : Howard C. Hang
language : en
Publisher: John Wiley & Sons
Release Date : 2023-02-06
Advanced Chemical Biology written by Howard C. Hang and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-02-06 with Science categories.
Advanced Chemical Biology The modern approach to teaching chemical biology Advanced Chemical Biology is organized around the central dogma of life, progressing from genes to proteins and higher-order cellular structures, including core application areas such as imaging, chemical genetics, activity-based protein profiling, and natural product discovery and biosynthesis. Advanced topics and applications in, e. g., microbiology, developmental biology, and neurobiology, are covered in separate sections. Every chapter is homogeneous in style and layout, consisting of a short historical introduction followed by a description of the underlying concepts and a selection of recent examples of how the concept has been turned into practice. The subdivision of the contents into core and supplemental chapters enables a flexible use in teaching, both for a one-semester and a two-semester course. Written by authors and editors coming from the leading scientific institutions that have developed the concepts and technologies for this discipline, Advanced Chemical Biology includes specific information on topics like: DNA function, synthesis and engineering, chemical approaches to genome integrity, and RNA function, synthesis, and probing Chemical approaches to transcription and RNA regulation in vivo, chemical biology of genome engineering, and peptide/protein synthesis and engineering Directed evolution for chemical biology, chemical biology of cellular metabolism, chemical biology of lipids, and protein post-translational modifications Chemical glycobiology, chemical and enzymatic modification of proteins, genetic code expansion, bio-orthogonal chemistry, and cellular imaging With its broad scope and focus on turning concepts into applications, Advanced Chemical Biology is an excellent starting point for anyone entering the field and looking for a guide to the wide range of available methods and strategies that chemical biology has to offer. With a Foreword by Nobel Laureate Carolyn Bertozzi.
Data Processing Handbook For Complex Biological Data Sources
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Author : Gauri Misra
language : en
Publisher: Academic Press
Release Date : 2019-03-23
Data Processing Handbook For Complex Biological Data Sources written by Gauri Misra and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-03-23 with Medical categories.
Data Processing Handbook for Complex Biological Data provides relevant and to the point content for those who need to understand the different types of biological data and the techniques to process and interpret them. The book includes feedback the editor received from students studying at both undergraduate and graduate levels, and from her peers. In order to succeed in data processing for biological data sources, it is necessary to master the type of data and general methods and tools for modern data processing. For instance, many labs follow the path of interdisciplinary studies and get their data validated by several methods. Researchers at those labs may not perform all the techniques themselves, but either in collaboration or through outsourcing, they make use of a range of them, because, in the absence of cross validation using different techniques, the chances for acceptance of an article for publication in high profile journals is weakened. Explains how to interpret enormous amounts of data generated using several experimental approaches in simple terms, thus relating biology and physics at the atomic level Presents sample data files and explains the usage of equations and web servers cited in research articles to extract useful information from their own biological data Discusses, in detail, raw data files, data processing strategies, and the web based sources relevant for data processing
Concepts And Case Studies In Chemical Biology
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Author : Herbert Waldmann
language : en
Publisher: John Wiley & Sons
Release Date : 2014-06-30
Concepts And Case Studies In Chemical Biology written by Herbert Waldmann and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-06-30 with Science categories.
Retaining the proven didactic concept of the successful "Chemical Biology - Learning through Case Studies", this sequel features 27 new case studies, reflecting the rapid growth in this interdisciplinary topic over the past few years. Edited by two of the world's leading researchers in the field, this textbook introduces students and researchers to the modern approaches in chemical biology, as well as important results, and the techniques and methods applied. Each chapter presents a different biological problem taken from everyday lab work, elucidated by an international team of renowned scientists. With its broad coverage, this is a valuable source of information for students, graduate students, and researchers working on the borderline between chemistry, biology, and biochemistry.
Visualizing Chemistry
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Author : National Research Council
language : en
Publisher: National Academies Press
Release Date : 2006-06-01
Visualizing Chemistry written by National Research Council and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-06-01 with Science categories.
Scientists and engineers have long relied on the power of imaging techniques to help see objects invisible to the naked eye, and thus, to advance scientific knowledge. These experts are constantly pushing the limits of technology in pursuit of chemical imagingâ€"the ability to visualize molecular structures and chemical composition in time and space as actual events unfoldâ€"from the smallest dimension of a biological system to the widest expanse of a distant galaxy. Chemical imaging has a variety of applications for almost every facet of our daily lives, ranging from medical diagnosis and treatment to the study and design of material properties in new products. In addition to highlighting advances in chemical imaging that could have the greatest impact on critical problems in science and technology, Visualizing Chemistry reviews the current state of chemical imaging technology, identifies promising future developments and their applications, and suggests a research and educational agenda to enable breakthrough improvements.
Water In Biological And Chemical Processes
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Author : Biman Bagchi
language : en
Publisher: Cambridge University Press
Release Date : 2013-11-14
Water In Biological And Chemical Processes written by Biman Bagchi and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-14 with Medical categories.
A unified overview of the dynamical properties of water and its unique and diverse role in biological and chemical processes.
Target Discovery And Validation
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Author : Alleyn T. Plowright
language : en
Publisher: John Wiley & Sons
Release Date : 2020-02-18
Target Discovery And Validation written by Alleyn T. Plowright and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-02-18 with Medical categories.
The modern drug developers? guide for making informed choices among the diverse target identification methods Target Discovery and Validation: Methods and Strategies for Drug Discovery offers a hands-on review of the modern technologies for drug target identification and validation. With contributions from noted industry and academic experts, the book addresses the most recent chemical, biological, and computational methods. Additionally, the book highlights techologies that are applicable to ?difficult? targets and drugs directed at multiple targets, including chemoproteomics, activity-based protein profiling, pathway mapping, genome-wide association studies, and array-based profiling. Throughout, the authors highlight a range of diverse approaches, and target validation studies reveal how these methods can support academic and drug discovery scientists in their target discovery and validation research. This resource: -Offers a guide to identifying and validating targets, a key enabling technology without which no new drug development is possible -Presents the information needed for choosing the appropriate assay method from the ever-growing range of available options -Provides practical examples from recent drug development projects, e. g. in kinase inhibitor profiling Written for medicinal chemists, pharmaceutical professionals, biochemists, biotechnology professionals, and pharmaceutical chemists, Target Discovery and Validation explores the current methods for the identification and validation of drug targets in one comrpehensive volume. It also includes numerous practical examples.
Environmental Health Perspectives
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Author :
language : en
Publisher:
Release Date : 2004
Environmental Health Perspectives written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Environmental health categories.
Metabolism Meets Function Untangling The Cross Talk Between Signalling And Metabolism
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Author : Alessandra Castegna
language : en
Publisher: Frontiers Media SA
Release Date : 2020-12-18
Metabolism Meets Function Untangling The Cross Talk Between Signalling And Metabolism written by Alessandra Castegna and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-12-18 with Medical categories.
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.