Systems Biology in Biotech & Pharma: A Changing Paradigm

ISBN-13: 9789400728486 / Angielski / Miękka / 2012 / 127 str.

Ale Prokop; Seth Michelson

Opis

Systems Biology (SB) is a suite of technologies and methodologies that resulted, conceptually from the merging of two basic paradigms, reductionism and holism with the goal of identifying its emergent properties and defining, quantitatively, molecular, cellular, tissue, organ and whole body processes. One manifestation of SB is as a tool for hypothesis generation about a system that is typically too large and complex to understand by simple reasoning.The US is currently well ahead of the rest of the world in the development and application of SB and its principles especially as they pertain to basic medical research and development.This lead is largely due to its earlier start in the academic arena. However, there is evidence of rapid development in both the UK/EU and Japan, and the gap is narrowing, particularly in the UK. From an industrial point of view, the Pharmaceutical Industry based in the US and UK can capitalize on these opportunities and gain the benefits of this technology. Many educational institutions (particularly their medical divisions) at present are heavily business-oriented, realize that in this particular industrial environment, that every dollar counts.This book intends to educate Cell and Molecular Biologists in the use of the quantitative tools that are available to them to help solve the critical problems they face. It is important that biologists recognize early in their research the use and benefits of SB and how this approach can help to generate new therapeutic leads and substances useful for human health. Educational curricula in the life sciences have typically been based on the belief that one can dissect complex systems into their components and that a detailed investigation of each these components individually will in itself lead to novel biological insights, and indeed this is true in numerous instances. However, increasing acknowledgment of the importance of studying whole systems, as well as their components, has led to an emphasis on teaching not just a reductionist view of biology, but also a complementary constructionist view. "

Spis treści

Abstract.- 1 Introduction: Discovery & Development - New Facet Of Industry, New Tools And Lead Optimization: 1.1 Scope And Content Of This Review.- 1.2 Drug Discovery & Development.- 1.3 Defining Sb:  Key Components.- 1.4  A Brief History Of Systems Biology (Sb), In Terms Of Key Advances.- 1.5 Perspective And Potential Impact Of Systems Biology On Academic Funding And Pharma R&D & Cost Savings.- 2 Discovery: Use Of Systems Biology For Identifying Targets: 2.1 Identifying Targets & Druggability Space.- 2.2 Combinatorial Chemistry Tools.- 2.3 Summarizing.- 3 Integrative Systems Biology I - Biochemistry:  Phase I Lead Discovery & Molecular Interactions.- 3.1 Molecular Screens: Receptor-Ligand (R-L) Interaction & Molecular Modeling.- 3.2 Collateral Efficacy & Permissive Antagonism.- 3.3 Co-Drugging:  Multiple Targets, Combination Therapy & Multistage Targeting.- 3.4 Text Mining For Interactions.- 3.5 Employment Of Biochemical Networks.- 3.6 Overview Of Deterministic Models.- 3.7 Bioinformatics.- 3.8 Summarizing.- 4 Integrative Systems Biology Ii - Molecular Biology:  Phase 2 Lead Discovery & In Silico Screening.- 4.1 Omics.- 4.2 Chemogenomics.- 4.3 Morphogenics.- 4.4 Minimal Phenotype & Synthetic Biology.- 4.5 Reconstructing Biological Networks.- 4.6 Summarizing.- 5. Discovery: Computational Systems Biology (Csb) In Health & And Disease I.- 5.1 Cellular Environment: Network Reconstruction & Inference From Experimental Data.- 5.2 Reconstructing Gene Networks.- 5.3 Data Mining And Heuristic Data Preprocessing Tools.- 5.4 Analysis Of Disease ‘Correlation Networktm’ And Concerted Metabolic Activation – Disease As A Systems Network Property.- 5.5 Challenges For Stem Cells:  Control.- 5.6 Emergent Properties.- 5.7 Computational Systems Biology.- 5.8 Summarizing.- 6 Development:  In Vivo Pharmacology - Systems Biology In Health & Disease Ii.- 6.1 Animal Disease Models.- 6.2 Pheno- And Genotyping.- 6.3 Rna Interference.- 6.4 Pharmacogenomics (Pgn).- 6.5 In Silico Pharmacology:  Future.- 6.6 Summarizing.- 7 Development: Pharmacokinetics – Systems Biology In Health & Disease Iii.- 7.1 Microdosing In Pk.- 7.2 Adaptive Trial Design.- 7.3 Equilibrium Vs. Non-Equilibrium Pk Models.- 7.5 Toxicity Biomarkers.- 7.6 In Silico Toxicity Prediction.- 7.7 Quantitative Pkpd/Tox Modeling.- 7.8 Summarizing.- 8 Development:  Multiscale Csb – Simulation Tools.- 8.1 Defining Csb.- 8.2 Redefining (& Discovering) Emergent Properties At  Higher-Level Hierarchies.- 8.3 Virtual Organs, Disease Models, Virtual Patient.- 8.4 Population Level Model:  Towards Individualized Medicine.- 8.5 Targeting Networks: Towards Organismic, Full-Scale Design.- 8.6 Redefining The Traditional R&D Paradigm.- 8.7 Summarizing.- 9 Development:  Drug Formulation & Delivery.- 9.1 Targeting Concept & Mechanisms.- 9.2 Nanoscale Drug Delivery Systems.- 9.3 Csb At Formulation & Delivery.- 9.4 Summarizing.- 10 Development: Preclinical Model Based Drug Development.- 10.1 Defining Mbdd.- 10.2 Summarizing.- 11 Systems Biology: Impact On Pharma And Biotech.- 11.1 Sb Impact.- 11.2 Key Technologies And Tools Needed For Development Of Systems Biology/Csb.- 11.3 Steps In Systems Biology/Csb.- 11.4 Benefits Of Systems Biology And Csb.- 11.5 Summary.- 12 Acknowledgment.- 13 Bibliography

Blurb

Systems Biology (SB) is a suite of technologies and methodologies that resulted, conceptually from the merging of two basic paradigms, reductionism and holism. It represents a combination of reductionist and holistic approaches to the relationships among the elements of a system, with the goal of identifying its emergent properties and defining, quantitatively, molecular, cellular, tissue, organ and whole body processes. One manifestation of SB is as a tool for hypothesis generation about a system that is typically too large and complex to understand by simple reasoning.