Phenotypic screening in the 21st century

Phenotypic screening in the 21st century PDF Author: Gul Erdemli
Publisher: Frontiers Media SA
ISBN: 2889194698
Category : Science (General)
Languages : en
Pages : 68

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Book Description
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

Phenotypic screening in the 21st century

Phenotypic screening in the 21st century PDF Author: Gul Erdemli
Publisher: Frontiers Media SA
ISBN: 2889194698
Category : Science (General)
Languages : en
Pages : 68

Get Book

Book Description
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

Toxicity Testing in the 21st Century

Toxicity Testing in the 21st Century PDF Author: National Research Council
Publisher: National Academies Press
ISBN: 0309151732
Category : Nature
Languages : en
Pages : 217

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Book Description
Advances in molecular biology and toxicology are paving the way for major improvements in the evaluation of the hazards posed by the large number of chemicals found at low levels in the environment. The National Research Council was asked by the U.S. Environmental Protection Agency to review the state of the science and create a far-reaching vision for the future of toxicity testing. The book finds that developing, improving, and validating new laboratory tools based on recent scientific advances could significantly improve our ability to understand the hazards and risks posed by chemicals. This new knowledge would lead to much more informed environmental regulations and dramatically reduce the need for animal testing because the new tests would be based on human cells and cell components. Substantial scientific efforts and resources will be required to leverage these new technologies to realize the vision, but the result will be a more efficient, informative and less costly system for assessing the hazards posed by industrial chemicals and pesticides.

Plant Genetic Resources for the 21st Century

Plant Genetic Resources for the 21st Century PDF Author: Kioumars Ghamkhar
Publisher: CRC Press
ISBN: 1000609685
Category : Technology & Engineering
Languages : en
Pages : 340

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Book Description
Exploring plant genetic resources is crucial in a time when food security has been a critical topic worldwide due to crop shortages and the impact of climate change. This new book, Plant Genetic Resources for the 21st Century: The OMICS Era, presents the practical advancements in genomics, epigenetics, metabolomics, and phenomics from the point of view of researchers and scientists working in the field of genebanks, genetics resources, and germplasm for enabling plant breeding and adaptation to a changing climate. The book highlights the importance of genebanks as centers of innovation for crop and forage improvement and discusses database solutions for genebanks and germplasm collections. The book first looks at plant genetic resources and their values and goes on to investigate several genomic technologies for plant improvement, conservation, and better adaptation to changing climates. Major crops such as wheat and barley are discussed with genomic approaches for diversity and resilience to drought and other adverse conditions. Other omics techniques discussed include phenomics for the improvement of crop adaptation, metabolomics research for germplasm improvement and adaptation, and more. This volume will be valuable for researchers who are presently working in or with genebanks and genetic resources, primarily for trait or allele discovery and germplasm improvement. Most chapters in the book can also be used as teaching material at the undergraduate and postgraduate levels.

Animal and Translational Models for CNS Drug Discovery: Neurological Disorders

Animal and Translational Models for CNS Drug Discovery: Neurological Disorders PDF Author: Robert A. McArthur
Publisher: Academic Press
ISBN: 9780080920382
Category : Medical
Languages : en
Pages : 416

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Book Description
Neurological Disorders is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for neurological disorders such as neurofibromatosis, Alzheimer’s disease, Parkinson’s disease, Huntington disease, ALS, and the epilepsies. Neurological Disorders has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. The aim of this series of volumes on Animal and Translational Models for CNS Drug Discovery is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery. This is the second volume in the three volume-set, Animal and Translational Models for CNS Drug Discovery 978-0-12-373861-5, which is also available for purchase individually. Clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery process Critical evaluation of animal and translational models improving transition from drug discovery and clinical development Emphasis on what results mean to the overall drug discovery process Exploration of issues in clinical trial design and conductance in each therapeutic area

Using 21st Century Science to Improve Risk-Related Evaluations

Using 21st Century Science to Improve Risk-Related Evaluations PDF Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309453518
Category : Nature
Languages : en
Pages : 201

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Book Description
Over the last decade, several large-scale United States and international programs have been initiated to incorporate advances in molecular and cellular biology, -omics technologies, analytical methods, bioinformatics, and computational tools and methods into the field of toxicology. Similar efforts are being pursued in the field of exposure science with the goals of obtaining more accurate and complete exposure data on individuals and populations for thousands of chemicals over the lifespan; predicting exposures from use data and chemical-property information; and translating exposures between test systems and humans. Using 21st Century Science to Improve Risk-Related Evaluations makes recommendations for integrating new scientific approaches into risk-based evaluations. This study considers the scientific advances that have occurred following the publication of the NRC reports Toxicity Testing in the 21st Century: A Vision and a Strategy and Exposure Science in the 21st Century: A Vision and a Strategy. Given the various ongoing lines of investigation and new data streams that have emerged, this publication proposes how best to integrate and use the emerging results in evaluating chemical risk. Using 21st Century Science to Improve Risk-Related Evaluations considers whether a new paradigm is needed for data validation, how to integrate the divergent data streams, how uncertainty might need to be characterized, and how best to communicate the new approaches so that they are understandable to various stakeholders.

PLANT BREEDING IN 21ST CENTURY

PLANT BREEDING IN 21ST CENTURY PDF Author: B.D. Singh
Publisher: Scientific Publishers
ISBN: 9389061288
Category : Science
Languages : en
Pages : 544

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Book Description
The discipline of plant breeding has undergone transformation due to the assimilation of the rapid developments in molecular biology. The existing books on plant breeding deal mainly with the classical approaches, while specialized books on molecular approaches usually lack discussion of the classical methods. The book Plant Breeding for 21st Century attempts to present the complete picture of plant breeding ranging from the classical to the molecular approaches applied to crop improvement. The book is divided into four sections: Classical Plant Breeding, Transgenic technology, Molecular Markers, and Miscellaneous. The first section deals with the classical plant breeding and is divided into eight chapters. The second section has four chapters and describes transgenic technology. The third section discusses various aspects of molecular markers and is spread over three chapters. The final section has a single chapter dealing with variety release, seed multiplication and intellectual property rights. This book is designed primarily for graduate students, viz., B.Sc. agriculture and B.Sc. science students with botany as one of the subjects, who would get their first exposure to plant breeding. It would also be useful for the post-graduate students, especially in botany, and to teachers of the subject. The book is written in simple and easy to understand language. Illustrations and photographs have been provided wherever they were expected to facilitate comprehension of the subject under discussion.

Trends in Cotton Breeding: Meeting the Challenges of the 21st Century

Trends in Cotton Breeding: Meeting the Challenges of the 21st Century PDF Author: Linghe Zeng
Publisher: Frontiers Media SA
ISBN: 2832501109
Category : Science
Languages : en
Pages : 297

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Book Description


Biological Nitrogen Fixation for the 21st Century

Biological Nitrogen Fixation for the 21st Century PDF Author: Claudine Elmerich
Publisher: Springer Science & Business Media
ISBN: 9401151598
Category : Science
Languages : en
Pages : 709

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Book Description
Nitrogen availability is one of the most critical factors that limits plant productivity. The largest reservoir of nitrogen is the atmosphere, but this gaseous molecular nitrogen only becomes available to plants through the biological nitrogen fixation process, which only prokaryotic cells have developed. The discovery that microbes were providing fixed nitrogen to legumes and the isolation of the first nitrogen-fixing bacteria occured at the end the 19th Century, in Louis Pasteur's time. We are now building on more than 100 years of research in this field and looking towards the 21st Century. The International Nitrogen Fixation Congress series Started more than 20 years ago. The format of this Congress is designed to gather scientists from very diverse origins, backgrounds, interests and scientific approaches and is a forum where fundamental knowledge is discussed alongside applied research. This confluence of perspectives is, we believe, extremely beneficial in raising new ideas, questions and concepts.

Theoretical and Applied Aspects of Systems Biology

Theoretical and Applied Aspects of Systems Biology PDF Author: Fabricio Alves Barbosa da Silva
Publisher: Springer
ISBN: 3319749749
Category : Computers
Languages : en
Pages : 259

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Book Description
This book presents the theoretical foundations of Systems Biology, as well as its application in studies on human hosts, pathogens and associated diseases. This book presents several chapters written by renowned experts in the field. Some topics discussed in depth in this book include: computational modeling of multiresistant bacteria, systems biology of cancer, systems immunology, networks in systems biology.

Genetics and Public Health in the 21st Century

Genetics and Public Health in the 21st Century PDF Author: Muin J. Khoury
Publisher: Oxford University Press, USA
ISBN: 0195128303
Category : Language Arts & Disciplines
Languages : en
Pages : 661

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Book Description
The first broad survey of these two fields, this book deleniates a framework for integrating advances in human genetics into public health practice.