Systems Biological Approaches in Infectious Diseases (eBook)

Helena I. Boshoff, Clifton E. Barry (Herausgeber)

eBook Download: PDF

2007 | 2007
IX, 350 Seiten
Springer Basel (Verlag)
978-3-7643-7567-6 (ISBN)

Infos

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.

Inhalt

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

Produkt-Details

• Erscheint lt. Verlag: 15.1.2007
• Reihe/Serie: Progress in Drug Research
• Reihe/Serie: Progress in Drug Research
• Zusatzinfo: IX, 350 p.
• Verlagsort: Basel
• Sprache: englisch
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Schlagworte: Anästhesie-Informations-Management-System • Antibiotics • Bacillus subtilis • Bacteria • Bacterial pathogens • Biology • Cells • Drug research • Dynamics • Genetics • Genome • Infectious • infectious disease • Infectious Diseases • Protein • systems biology • Toxicology
• ISBN-10: 3-7643-7567-1 / 3764375671
• ISBN-13: 978-3-7643-7567-6 / 9783764375676