| The Phage Nanoparticle Toolkit | p. 1 |
| Introduction | p. 1 |
| Virion Structure and Purification | p. 1 |
| Intrusion | p. 4 |
| DNA Replication Cycle and Gene Expression | p. 5 |
| Extrusion of Progeny Virions | p. 6 |
| Display of Guest Peptides | p. 7 |
| The Engineer's Toolkit | p. 8 |
| Acknowledgements | p. 10 |
| References | p. 10 |
| The Roles of Structure, Dynamics and Assembly in the Display of Peptides on Filamentous Bacteriophage | p. 12 |
| Molecular and Structural Biology of Filamentous Bacteriophage | p. 12 |
| Packaging of the Genome into Filamentous Bacteriophage | p. 14 |
| Structural Form of the Major Coat Protein | p. 16 |
| Membrane-bound Form of Filamentous Bacteriophage Coat Proteins | p. 21 |
| Assembly | p. 24 |
| Phage Display | p. 25 |
| Conclusion | p. 29 |
| Acknowledgements | p. 29 |
| References | p. 30 |
| Quantitative Analysis of Peptide Libraries | p. 33 |
| Introduction | p. 33 |
| Assessing the Quality of a Phage-displayed Library | p. 35 |
| Peptide Sequence Censorship | p. 35 |
| Experimental Measures | p. 36 |
| Conceptual Measures | p. 36 |
| Quantitative Measures | p. 37 |
| Assessing the Quality of an Affinity Screen Experiment | p. 42 |
| Change in Diversity | p. 43 |
| Change in Information | p. 43 |
| Identification of Motifs in a Peptide Population | p. 45 |
| Similarity Matrices | p. 45 |
| Identification of Binding Sites in Proteins | p. 47 |
| Identification of Binding Proteins in a Proteome | p. 50 |
| Relic | p. 51 |
| Discussion | p. 53 |
| References | p. 53 |
| Phage-mediated Drug Delivery | p. 55 |
| Introduction | p. 55 |
| Targeting of Drugs/Drug Carrier Systems | p. 58 |
| Targeting Ligands | p. 59 |
| Phage-displayed Libraries as a Source of Peptide Targeting Ligands | p. 60 |
| Bacteriophage Capsid-mediated Drug Delivery | p. 62 |
| Drug-bearing Filamentous Phage as Targeted Chemotherapeutics | p. 67 |
| Phage Fusion Proteins as Targeting Ligands for Nanomedicines | p. 70 |
| Conclusion | p. 77 |
| Acknowledgements | p. 78 |
| References | p. 78 |
| Imaging with Bacteriophage-derived Probes | p. 83 |
| Selection of Bacteriophage as Imaging Probes | p. 83 |
| Imaging Agents | p. 83 |
| Phage Nanoparticles | p. 85 |
| Phage Display for Imaging Probe Discovery | p. 85 |
| Radiolabled Phage as Imaging Agents | p. 87 |
| Optical Molecular Imaging with Phage | p. 93 |
| Conclusion | p. 97 |
| References | p. 97 |
| Phage-based Pathogen Biosensors | p. 101 |
| Introduction | p. 101 |
| Threat of Pathogenic Microorganisms | p. 101 |
| Pathogen Detection Techniques | p. 102 |
| Current Trends and Existing Methodologies for Pathogen Detection | p. 103 |
| Conventional Pathogen Detection Techniques | p. 103 |
| Polymerase Chain Reaction (PCR) | p. 104 |
| Enzyme-linked Immunosorbent Assay (ELISA) | p. 105 |
| Biosensor Techniques | p. 107 |
| Biomolecular Recognition Element | p. 108 |
| Whole Filamentous Bacteriophage Particles as a Biorecognition Probe | p. 110 |
| Phage Immobilization on Biosensor Platforms | p. 112 |
| Current Trends in Development of Phage-based Biosensors | p. 118 |
| Phage-based Magnetoelastic Particle Resonator Biosensors | p. 126 |
| Magnetoelastic (ME) Particle Resonator Sensor Platform | p. 126 |
| Fabrication of the Sensor Platform | p. 129 |
| ME Biosensor Assembly | p. 132 |
| Performance of Phage-based ME Biosensors | p. 133 |
| Conclusion | p. 148 |
| Acknowledgements | p. 148 |
| References | p. 149 |
| Phage-mediated Detection of Biological Threats | p. 156 |
| Introduction | p. 156 |
| Phage Typing Schemes | p. 157 |
| Exploiting Phage Specificity for Bacterial Detection | p. 158 |
| Labeled Phage | p. 158 |
| Reprter Phage | p. 159 |
| Phage Amplification | p. 166 |
| Electrochemical-based Sensing Assays | p. 170 |
| Surface Plasmon Resonance-based Sensing Assays | p. 171 |
| The Phage-mediated Adenylate Kinase Assay | p. 171 |
| Conclusion | p. 172 |
| References | p. 172 |
| Genetically Engineered Virulent Phage Banks for the Detection and Control of Bacterial Biosecurity Threats | p. 175 |
| Introduction | p. 175 |
| Host Range engineering | p. 179 |
| Production of a Genetically Engineered T4 Phage Bank with Vastly Increased Host Range | p. 183 |
| Reversible Inhibition of the T4 Lytic Cycle Within the Bacterial Host | p. 183 |
| Large-scale Recombinations into the Genomes of an Infective Wild-type T4 Population | p. 188 |
| Construction of a T4 Bank of Host Range Variants | p. 190 |
| Discussion | p. 190 |
| Conclusion and Perspectives | p. 194 |
| Methods | p. 195 |
| High-fidelity PCR | p. 195 |
| Error-prone PCR | p. 195 |
| Selective High-fidelity Amplification of Desired Fragments | p. 198 |
| Reconstruction of Sequence Through PCR | p. 198 |
| DNA Sequencing and Analysis | p. 199 |
| Production and Expression of Non-functional E. coli Rho Genes | p. 199 |
| Construction and Expression of the Heat-inducible Red-Recombinase System | p. 199 |
| Acknowledgements | p. 199 |
| References | p. 200 |
| Site-directed Chemical Modification of Phage Particles | p. 202 |
| Introduction | p. 202 |
| Unique Chemical Properties of Selenocysteine Compared with Cysteine | p. 203 |
| In vivo Incorporation of Sec by E. coli | p. 205 |
| Construction of Selenopeptide-displayed Phage Libraries | p. 207 |
| Applications Using Selenopeptide Phage Display | p. 209 |
| Screening for Sec Insertion in vivo: Investigating the Stringency of E. coli SECIS Requirements Using Phage Display | p. 209 |
| Catalysis-based Selection of Novel Enzyme Activities from Substrate-appended Phage Libraries | p. 212 |
| Mechanical Manipulation of M13 Phage | p. 215 |
| Conclusion | p. 216 |
| References | p. 216 |
| Filamentous Fhage-templated Synthesis and Assembly of Inorganic Nanomaterials | p. 220 |
| Introduction | p. 220 |
| Virion Structure and Phage Display | p. 221 |
| Biology | p. 221 |
| Chemistry | p. 224 |
| Site-specific Engineering of the Virion Surface | p. 225 |
| Liquid Crystalline Behavior | p. 225 |
| Exploiting Phage Display to Alter Surface Chemistry by Selection Rather Than Rational Design225 | |
| Random Peptide Libraries225 | |
| Affinity Selection ('Biopanning')226 | |
| Synthesis and Assembly of Inorganic Materials on Individual Virions | p. 227 |
| Synthesis and Assembly of Inorganic Materials on a Self-assembled Phage Scaffold | p. 231 |
| Applications of Phage-templated Nanomaterials | p. 234 |
| Summary and Outlook | p. 239 |
| Acknowledgements | p. 240 |
| References | p. 240 |
| Phage Vaccines and Phage Therapy | p. 245 |
| Introduction to Phage | p. 245 |
| Phage Immunogens | p. 246 |
| Epitope Discovery with Phage Libraries and Phage Vaccines | p. 248 |
| Autoimmune Disorders | p. 251 |
| Cancer | p. 251 |
| Neurological Disorders | p. 252 |
| Other Diseases | p. 252 |
| Antibacterial Therapy | p. 253 |
| Conclusion | p. 255 |
| References | p. 256 |
| Subject Index | p. 259 |
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