Chemical Biology of the Genome provides a comprehensive overview of essential concepts and principles of genomic and epigenomics dynamics as explored through the lens of chemical biology. Key examples and case studies illustrate chemical biology methods for study and analysis of the genome and epigenome, with an emphasis on relevance to physiological and pathophysiological processes and drug discovery. Authors and international leaders in biochemical studies of the genome, Drs. Siddhartha Roy and Tapas Kundu, adopt an integrated, interdisciplinary approach throughout, demonstrating how fast evolving chemical and mass-scale sequencing tools are increasingly used to interpret biochemical processes of the genome. Later sections discuss chemical modifications of the genome, DNA sequence recognition by proteins and gene regulation, GWAS and EpiGWAS studies, 3D architecture of the genome, and functional genome architecture. In-depth, discovery focused chapters examine intervention in gene networks using SiRNA/ShRNA, miRNA, and anti-miR, small molecule modulation of iPS, drug resistance pathways altered DNA methylation as drug targets, anti-miR as therapeutics, and nanodelivery of drugs. Offers an interdisciplinary discussion of the chemical biology of the genome and epigenome, employing illustrative case studies in both physiological and pathophysiological contexts Supports researchers in employing chemical and mass-scale sequencing approaches to interpret genomic and epigenomic dynamics Highlights innovative pathways and molecular targets for new disease study and drug discovery

This book focuses on an “outside the box” notion by utilizing the powerful applications of next-generation sequencing (NGS) technologies in the interface of chemistry and biology. In personalized medicine, developing small molecules targeting a specific genomic sequence is an attractive goal. N-methylpyrrole (P)–N-methylimidazole (I) polyamides (PIPs) are a class of small molecule that can bind to the DNA minor groove. First, a cost-effective NGS (ion torrent platform)-based Bind-n-Seq was developed to identify the binding specificity of PIP conjugates in a randomized DNA library. Their biological influences rely primarily on selective DNA binding affinity, so it is important to analyze their genome-wide binding preferences. However, it is demanding to enrich specifically the small-molecule-bound DNA without chemical cross-linking or covalent binding in chromatinized genomes. Herein is described a method that was developed using high-throughput sequencing to map the differential binding sites and relative enriched regions of non-cross-linked SAHA-PIPs throughout the complex human genome. SAHA-PIPs binding motifs were identified and the genome-level mapping of SAHA-PIPs-enriched regions provided evidence for the differential activation of the gene network. A method using high-throughput sequencing to map the binding sites and relative enriched regions of alkylating PIP throughout the human genome was also developed. The genome-level mapping of alkylating the PIP-enriched region and the binding sites on the human genome identifies significant genomic targets of breast cancer. It is anticipated that this pioneering low-cost, high through-put investigation at the sequence-specific level will be helpful in understanding the binding specificity of various DNA-binding small molecules, which in turn will be beneficial for the development of small-molecule-based drugs targeting a genome-level sequence.

Advances in chemistry, biology and genomics coupled with laboratory automation and computational technologies have led to the rapid emergence of the multidisciplinary field of chemical genomics. This edited text, with contributions from experts in the field, discusses the new techniques and applications that help further the study of chemical genomics. The beginning chapters provide an overview of the basic principles of chemical biology and chemical genomics. This is followed by a technical section that describes the sources of small-molecule chemicals; the basics of high-throughput screening technologies; and various bioassays for biochemical-, cellular- and organism-based screens. The final chapters connect the chemical genomics field with personalized medicine and the druggable genome for future discovery of new therapeutics. This book will be valuable to researchers, professionals and graduate students in many fields, including biology, biomedicine and chemistry.

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.

Chemical genomics is a highly interdisciplinary and very exciting field of research both in academics and in the life sciences industry. The Ernst Schering Research Foundation Workshop 58 was organized to bring together scientific leaders in the field to discuss the implications of chemical genomics for drug discovery. Various aspects of the interface between chemistry and biology are covered in this volume, such as chemogenomics efforts in the pharmaceutical industry, diversity-oriented synthesis, chemogenomic approaches to the study of cell function, screening technologies, and natural products as tools in chemical biology.

Never before has it been so critical for lab workers to possess the proper tools and methodologies necessary to determine the structure, function, and expression of the corresponding proteins encoded in the genome. Mulhardt's Molecular Biology and Genomics helps aid in this daunting task by providing the reader with tips and tricks for more successful lab experiments. This strategic lab guide explores the current methodological variety of molecular biology and genomics in a simple manner, addressing the assets and drawbacks as well as critical points. It also provides short and precise summaries of routine procedures as well as listings of the advantages and disadvantages of alternative methods. Shows how to avoid experimental dead ends and develops an instinct for the right experiment at the right time Includes a handy Career Guide for researchers in the field Contains more than 100 extensive figures and tables

Biological and chemical sciences have undergone an unprecedented transformation, reflected by the huge use of parallel and automated technologies in key fields such as genome sequencing, DNA chips, nanoscale functional biology or combinatorial chemistry. It is now possible to generate and store from tens of thousands to millions of new small molecules, based on enhanced chemical synthesis strategies. Automated screening of small molecules is one of the technologies that has revolutionized biology, first developed for the pharmaceutical industry and recently introduced in academic laboratories. High-throughput and high-content screening allow the identification of bioactive compounds in collections of molecules (chemical libraries), being effective on biological targets defined at various organisational scales, from proteins to cells to complete organisms. These bioactive molecules can be therapeutic drug candidates, molecules for biotech, diagnostic or agronomic applications, or tools for basic research. Handling a large number of biological (genomic and post-genomic), chemical and experimental information, screening approaches cannot be envisaged without any electronic storage and mathematical treatment of the data. “Chemogenomics and Chemical Genetics” is an introductory manual presenting methods and concepts making up the basis for this recent discipline. This book is dedicated to biologists, chemists and computer scientist beginners. It is organized in brief, illustrated chapters with practical examples. Clear definitions of biological, chemical and IT concepts are given in a glossary section to help readers who are not familiar with one of these disciplines. "Chemogenomics and Chemical Genetics" should therefore be helpful for students (from Bachelor's degree level), technological platform engineers, and researchers in biology, chemistry, bioinformatics, cheminformatics, both in biotech and academic laboratories.