Phenotypic Screening In The 21st Century

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

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.

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.

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.

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.

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.

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