Jucker Systems Biological Approaches in Infectious Diseases

1. Auflage 2007
ISBN: 978-3-7643-7567-6
Verlag: Springer
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 350 Seiten

This book brings together the various fields of functional genomics and systems biology that provide information on metabolic function. There is special emphasis on the identification of drug targets. The book includes practical examples from the various 'omic' sciences as well as theoretical examples of how integrated knowledge of these sciences can be applied to drug discovery. It is of interest to researchers in the pharmaceutical drug discovery environment.

Autoren/Hrsg.

Jucker, Ernst

Inhaltsverzeichnis

1;Foreword;8
2;Systems biology and its impact on anti- infective drug development;11
2.1;1 Introduction;12
2.2;2 Data for systems biology: ‘Omics, images and chemistry;14
2.3;3 Makingmodels;16
2.4;4 Networks;18
2.5;5 Integrative systems biology;23
2.6;6 New targets for anti-infective drug development;24
2.7;References;26
3;Applications of transcriptional profiling in antibiotics discovery and development;30
3.1;1 Introduction;31
3.2;2 Transcriptional profiling – highly parallel measurement of gene expression;32
3.3;3 Comparison of the capabilities of transcriptomics and proteomics;35
3.4;4 The importance of experimental design and integrated data analysis systems;35
3.5;5 Discovering therapeutic targets;37
3.6;6 Forward pharmacology;40
3.7;7 Developing reporter assays for pathway-specific compound screens;43
3.8;8 Improving the compound selection and optimization process;45
3.9;9 Assessing drug safety and toxicology;47
3.10;10 Conclusion;48
3.11;References;50
4;Chemical genetics: An evolving toolbox for target identification and lead optimization;56
4.1;1 Genomic approaches to identifying drug targets;57
4.2;2 The genomic interface of chemistry and biology: Chemical genetics;58
4.3;3 Conclusion: Chemical genetics and drug development;78
4.4;References;78
5;Proteomic profiling of cellular stresses in Bacillus subtilis reveals cellular networks and assists in elucidating antibiotic mechanisms of action;84
5.1;1 Introduction;85
5.2;2 The tools of proteomic profiling;87
5.3;3 Proteomic contributions to understanding bacterial physiology;91
5.4;4 Proteomics in antibacterial drug discovery;95
5.5;References;102
6;Elucidating the mode- of- action of compounds from metabolite profiling studies;106
6.1;1 Introduction;107
6.2;2 Microbial metabolite profiling;108
6.3;3 Novel drug discovery;121
6.4;4 In vivo metabolic fluxes;122
6.5;5 Metabolites in systems biology;124
6.6;References;126
7;A subsystems-based approach to the identification of drug targets in bacterial pathogens;132
7.1;1 Introduction;133
7.2;2 Stage I: Choosing target subsystems. Genome- scale essentiality and conservation analysis;136
7.3;3 Stage II: Analyzing target subsystems. Metabolic reconstruction and functional predictions;146
7.4;4 Stage III: Selecting target genes. Target prioritization and validation;158
7.5;5 Concluding remarks: From targets to drugs;162
7.6;References;164
8;Metabolic control analysis to identify optimal drug targets;171
8.1;1 Introduction;172
8.2;2 Mathematical models: Assistants for the human brain;173
8.3;3 Metabolic control analysis: Basic principles;175
8.4;4 Effective drug target identification using MCA;179
8.5;5 Enhancing anti-parasite drug selectivity with differential control analysis;180
8.6;6 Control of tumor cell growth;183
8.7;References;185
9;The protein network as a tool for finding novel drug targets;189
9.1;1 Protein linkages;190
9.2;2 Biochemical methods to identify protein-protein interactions;190
9.3;3 Computational methods to identify protein linkages;192
9.4;4 Protein networks;195
9.5;5 Drug targets;203
9.6;6 Conclusion;207
9.7;References;208
10;Toxicogenomics applied to predictive and exploratory toxicology for the safety assessment of new chemical entities: a long road with deep potholes;213
10.1;1 Overview;214
10.2;2 Toxicogenomics;216
10.3;3 Conclusion;229
10.4;References;230
11;Biological robustness in complex host- pathogen systems;234
11.1;1 Robustness is a fundamental organizational principle of biological systems;235
11.2;2 Four underlying general mechanisms for robustness;237
11.3;3 Intrinsic features of robust systems: Evolvability and trade- offs;239
11.4;4 Robustness attributes of pathogens;241
11.5;5 Limits of a robust system: Pathogen-triggered diseases;244
11.6;6 Does microbial flora affect vulnerability against pathogenic infections?;248
11.7;7 Future directions;250
11.8;References;251
12;Toward whole cell modeling and simulation: Comprehensive functional genomics through the constraint- based approach;258
12.1;1 Introduction to modeling using the constraint- based approach;259
12.2;2 Building a constraint-based model;262
12.3;3 Metabolic model applications and computational challenges;276
12.4;4 Future directions for constraint-based modeling;283
12.5;5 Conclusions;294
12.6;References;294
13;Genomics of host- pathogen interactions;302
13.1;1 Introduction;303
13.2;2 Functional genomics of bacterial pathogens;303
13.3;3 RNA profiling of host cells after infections;317
13.4;4 Functional genomics and drug discovery;321
13.5;References;324