An introduction to molecular biotechnology: fundamentals, methods, and applications
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Weinheim
Wiley-VCH
2011
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| Edition: | 2., updated ed. |
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| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXXIII, 601 S. Ill., graph. Darst. |
| ISBN: | 9783527326372 |
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| 245 | 1 | 0 | |a An introduction to molecular biotechnology |b fundamentals, methods, and applications |c ed. by Michael Wink |
| 250 | |a 2., updated ed. | ||
| 264 | 1 | |a Weinheim |b Wiley-VCH |c 2011 | |
| 300 | |a XXXIII, 601 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 0 | 7 | |a Biotechnologie |0 (DE-588)4069491-4 |2 gnd |9 rswk-swf |
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| adam_text | IMAGE 1
CONTENTS
PREFACE XIX
LIST OF CONTRIBUTORS XXI
ABBREVIATIONS XXV
PARTI FUNDAMENTALS OF CELLULAR AND MOLECULAR BIOLOGY 1
1 THE CELL AS THE BASIC UNIT OF LIFE 3
M. WINK
2 STRUCTURE AND FUNCTION OF CELLULAR MACROMOLECULES 7 M. WINK 2.1
STRUCTURE AND FUNCTION OF SUGARS 8
2.2 STRUCTURE OF MEMBRANE LIPIDS 10
2.3 STRUCTURE AND FUNCTION OF PROTEINS 14
2.4 STRUCTURE OF NUCLEOTIDES AND NUCLEIC ACIDS (DNA AND RNA) 21 2.5
REFERENCES 27
3 STRUCTURE AND FUNCTIONS OF A CELL 29 M. WINK 3.1 STRUCTURE OF A
EUKARYOTIC CELL 29
3.1.1 STRUCTURE AND FUNCTION OF THE CYTOPLASMIC MEMBRANE 29 3.1.1.1
MEMBRANE PERMEABILITY 30 3.1.1.2 TRANSPORT PROCESSES ACROSS BIOMEMBRANES
31
3.1.1.3 RECEPTORS AND SIGNAL TRANSDUCTION AT BIOMEMBRANES 33 3.1.2
ENDOMEMBRANE SYSTEM IN A EUKARYOTIC CELL 38 3.1.3 MITOCHONDRIA AND
CHLOROPLASTS 40 3.1.4 CYTOPLASM 45
3.1.5 CYTOSKELETON 47
3.1.6 CELL WALLS 49
3.2 STRUCTURE OF BACTERIA 50
3.3 STRUCTURE OF VIRUSES 51
3.4 DIFFERENTIATION OF CELLS 52
4 BIOSYNTHESIS AND FUNCTION OF MACROMOLECULES (DNA, RNA, AND PROTEINS)
57 M. WINK 4.1 GENOMES, CHROMOSOMES, AND REPLICATION 57 4.1.1 GENOME
SIZE 57
4.1.2 COMPOSITION AND FUNCTION OF CHROMOSOMES 62 4.1.3 MITOSIS AND
MEIOSIS 64
4.1.4 REPLICATION 66
4.1.5 MUTATIONS AND REPAIR MECHANISMS 66
BIBLIOGRAFISCHE INFORMATIONEN HTTP://D-NB.INFO/1009330500
DIGITALISIERT DURCH
IMAGE 2
VI I CONTENTS
4.2 TRANSCRIPTION: FROM GENE TO PROTEIN 71
4.3 PROTEIN BIOSYNTHESIS (TRANSLATION) 76
5 DISTRIBUTING PROTEINS IN THE CELL (PROTEIN SORTING) 81 M. WINK 5.1
IMPORT AND EXPORT OF PROTEINS VIA THE NUCLEAR PORE 82 5.2 IMPORT OF
PROTEINS IN MITOCHONDRIA AND CHLOROPLASTS 83 5.3 PROTEIN TRANSPORT INTO
THE ENDOPLASMIC RETICULUM 85 5.4 VESICLE TRANSPORT FROM THE ER VIA THE
GOLGI APPARATUS TO THE CYTO-
PLASMIC MEMBRANE 86
6 EVOLUTION AND DIVERSITY OF ORGANISMS 91 M. WINK 6.1 PROKARYOTES 91
6.2 EUKARYOTES 93
PART II STANDARD METHODS IN MOLECULAR BIOTECHNOLOGY 99
7 ISOLATION AND PURIFICATION OF PROTEINS 101 T. WIELAND, M. LUTZ 7.1
INTRODUCTION 101
7.2 PRODUCING A PROTEIN EXTRACT 102
7.3 GEL ELECTROPHORETIC SEPARATION METHODS 103 7.3.1 PRINCIPLES OF
ELECTROPHORESIS 103 7.3.2 NATIVE GEL ELECTROPHORESIS 104 7.3.3
DISCONTINUOUS SODIUM DODECYL SULFATEPOLYACRYLAMIDE
GEL ELECTROPHORESIS (SDS-PAGE) 104 7.3.4 TWO-DIMENSIONAL (2D) GEL
ELECTROPHORESIS, ISOELECTRIC FOCUSING (IEF) 105 7.3.5 DETECTING PROTEINS
IN GELS 105
7.4 METHODS OF PROTEIN PRECIPITATION 106 7.5 COLUMN CHROMATOGRAPHY
METHODS 107 7.5.1 GENERAL PRINCIPLES OF SEPARATION 107 7.5.1.1 SIZE
EXCLUSION CHROMATOGRAPHY (GEL FILTRATION) 107 7.5.1.2 HYDROPHOBIE
INTERACTION CHROMATOGRAPHY 108
7.5.1.3 ION EXCHANGE CHROMATOGRAPHY 109 7.5.1.4 HYDROXYAPATITE
CHROMATOGRAPHY 110 7.5.2 GROUP-SPECIFIC SEPARATION TECHNIQUES 110
7.5.2.1 CHROMATOGRAPHY ON PROTEIN A OR PROTEIN G 110 7.5.2.2
CHROMATOGRAPHY ON CIBACRON BLUE (BLUE GEL) 111 7.5.2.3 CHROMATOGRAPHY ON
LECTINS 111 7.5.2.4 CHROMATOGRAPHY ON HEPARIN 111
7.5.3 PURIFICATION OF RECOMBINANT FUSION PROTEINS 112 7.5.3.1
CHROMATOGRAPHY ON CHELATING AGENTS 112 7.5.3.2 CHROMATOGRAPHY ON
GLUTATHIONE MATRICES 112 7.6 EXAMPLES 113
7.6.1 EXAMPLE 1: PURIFICATION OF NUCLEOSIDE DIPHOSPHATE KINASE FROM THE
CYTOSOL OF BOVINE RETINA ROD CELLS 113 7.6.2 EXAMPLE 2: PURIFICATION OF
RECOMBINANT HIS 6 -RGS16 AFTER EXPRESSION IN E. COLI 114
8 PEPTIDE AND PROTEIN ANALYSIS WITH ELECTROSPRAY TANDEM MASS
SPECTROMETRY 115 A. SCHLOSSER, W. D. LEHMANN 8.1 INTRODUCTION 315
8.2 PRINCIPLES OF MASS SPECTROMETRY 115 8.3 MASS PRECISION, RESOLUTION,
AND ISOTOPE DISTRIBUTION 136
IMAGE 3
CONTENTS VII
8.4 PRINCIPLES OF ESI 336
8.5 TANDEM MASS SPECTROMETERS 117 8.5.1 MASS ANALYZERS 117
8.5.2 TRIPLE QUADRUPOLE 118 8.5.3 LINEAR TRAP QUADRUPOLE (LTQ) AND LTQ
ORBITRAP 338 8.5.4 Q-TOF 339
8.5.5 Q-FT-ICR 119
8.6 PEPTIDE SEQUENCING WITH MS/MS 339 8.7 IDENTIFYING PROTEINS WITH
MS/MS DATA AND PROTEIN DATABASES 120 8.7.1 DATABASE SEARCH WITH MS/MS
RAW DATA 120 8.8 DETERMINING PROTEIN MOLECULAR MASS 121 8.9 ANALYSIS OF
COVALENT PROTEIN MODIFICATION 122 8.10 RELATIVE AND ABSOLUTE
QUANTIFICATION 123
9 ISOLATION OF DNA AND RNA 325
H. WEIHER, R. ZWACKA, I. HERR 9.1 INTRODUCTION 325
9.2 DNA ISOLATION 325
9.3 RNA ISOLATION 127
9.3.1 ENRICHMENT OF MRNA 127
10 CHROMATOGRAPHY AND ELECTROPHORESIS OF NUCLEIC ACIDS 329 H. WEIHER, R.
ZWACKA, I. HERR 10.1 INTRODUCTION 329
10.2 CHROMATOGRAPHIE SEPARATION OF NUCLEIC ACIDS 129 10.3
ELECTROPHORESIS 330
10.3.1 AGAROSE GEL ELECTROPHORESIS: SUBMARINE ELECTROPHORESIS 330 10.3.2
PULSED FIELD AGAROSE GEL ELECTROPHORESIS 333 10.3.3 POLYACRYLAMIDE GEL
ELECTROPHORESIS (PAGE) 333
11 HYBRIDIZATION OF NUCLEIC ACIDS 133 H. WEIHER, R. ZWACKA, I. HERR 11.1
SIGNIFICANCE OF BASE PAIRING 333 11.2 EXPERIMENTAL HYBRIDIZATION:
KINETIC
AND THERMODYNAMIC CONTROL 133 11.3 ANALYTICAL TECHNIQUES 334 11.3.1
CLONE DETECTION, SOUTHERN BLOTTING, NORTHERN BLOTTING,
AND GENE DIAGNOSIS 334 11.3.2 SYSTEMATIC GENE DIAGNOSIS AND EXPRESSION
SCREENING BASED ON GENE ARRAYS 335 11.3.3 IN SITU HYBRIDIZATION 335
12 USE OF ENZYMES IN THE MODIFICATION OF NUCLEIC ACIDS 337 A. GROTH, R.
ZWACKA, H. WEIHER, I. HERR 12.1 RESTRICTION ENZYMES (RESTRICTION
ENDONUCLEASES) 337 12.2 LIGASES 339
12.3 METHYLTRANSFERASES 139 12.4 DNA POLYMERASES 140
12.5 RNA POLYMERASES AND REVERSE TRANSCRIPTASE 343 12.6 NUCLEASES 343
12.7 T4 POLYNUCLEOTIDE KINASE 141 12.8 PHOSPHATASES 142
13 POLYMERASE CHAIN REACTION 343 A. MOHR, H. WEIHER, I. HERR, R. ZWACKA
13.1 INTRODUCTION 143
13.2 TECHNIQUES 143
IMAGE 4
VIII CONTENTS
13.2.1 STANDARD PCR 143
13.2.2 RT-PCR 144 13.2.3 QUANTITATIVE/REAL-TIME PCR 145 13.2.4 RAPID
AMPLIFICATION OF CDNA ENDS (RACE) 346 13.3 AREAS OF APPLICATION 146
13.3.1 GENOME ANALYSIS 146 13.3.2 CLONING TECHNIQUES 147 13.3.3
EXPRESSION STUDIES 147
14 DNA SEQUENCING 149
R. ZWACKA, A. MOHR, I. HERR, H. WEIHER 14.1 INTRODUCTION 349
14.2 DNA SEQUENCING METHODS 149 14.2.1 CHEMICAL SEQUENCING METHOD
(MAXAMGILBERT METHOD) 350 14.2.2 ENZYMATIC SEQUENCING (SANGERCOULSON
METHOD) 350 14.2.3 PYROSEQUENCING 151 14.3 STRATEGIES FOR SEQUENCING THE
HUMAN GENOME 151 14.4 PRACTICAL SIGNIFICANCE OF DNA 152
15 CLONING PROCEDURES 153 T. WIELAND, S. LUTZ 15.1 INTRODUCTION 353
15.2 CONSTRUCTION OF RECOMBINANT VECTORS 153 15.2.1 INSERT 154
15.2.2 VECTOR 156
15.2.3 ESSENTIAL COMPONENTS OF VECTORS 156 15.2.3.1 BACTERIAL ORIGIN OF
REPLICATION (ORI) 156 15.2.3.2 ANTIBIOTIC RESISTANCE 156 15.2.3.3
POLYLINKERS 357
15.2.4 CLONING USING RECOMBINATION SYSTEMS 157 15.2.5 FURTHER COMPONENTS
OF VECTORS FOR PROKARYOTIC EXPRESSION SYSTEMS 158 15.2.5.1 PROMOTER 158
15.2.5.2 RIBOSOME-BINDING SITE 359 15.2.5.3 TERMINATION SEQUENCE 159
15.2.5.4 FUSION SEQUENCE 159 15.2.6 FURTHER COMPONENTS OF EUKARYOTIC
EXPRESSION VECTORS 359
15.2.6.1 EUKARYOTIC EXPRESSION VECTORS: YEAST 360 15.2.6.2 EUKARYOTIC
EXPRESSION VECTORS FOR MAMMAL CELLS 363 15.2.6.3 VIRAL EXPRESSION
SYSTEMS FOR MAMMALIAN CELLS 363 15.2.7 NONVIRAL INTRODUCTION OF
HETEROLOGOUS DNA TO HOST ORGANISMS
(TRANSFORMATION, TRANSFECTION) 165 15.2.7.1 TRANSFORMATION OF
PROKARYOTES 165 15.2.7.2 TRANSFORMATION OF YEAST CELLS 366 15.2.7.3
TRANSFECTION OF MAMMAL CELLS 166
16 EXPRESSION OF RECOMBINANT PROTEINS 369 T. WIELAND, S. LUTZ 16.1
INTRODUCTION 369
16.2 EXPRESSION OF RECOMBINANT PROTEINS IN HOST ORGANISMS 370 16.2.1
EXPRESSION IN E. COLI 173 16.2.2 EXPRESSION IN YEASTS 374 16.2.3
EXPRESSION IN INSECT CELLS 376
16.2.3.1 EXPRESSION BASED ON RECOMBINANT BACULOVIRUSES 376 16.2.3.2
EXPRESSION OF PROTEINS IN STABLY TRANSFECTED INSECT CELLS 177 16.2.4
EXPRESSION OF PROTEINS IN MAMMALIAN CELLS 377 16.3 EXPRESSION IN
CELL-FREE SYSTEMS 378
IMAGE 5
CONTENTS I IX
16.3.1 EXPRESSION OF PROTEINS IN RETICULOCYTE LYSATES 379
16.3.2 PROTEIN EXPRESSION USING E. COLI EXTRACTS 179
17 PATCH CLAMP METHOD 181
R. KRAFT
17.1 BIOLOGICAL MEMBRANES AND ION CHANNELS 383 17.2 PHYSICAL FOUNDATIONS
OF THE PATCH CLAMP METHOD 382 17.3 PATCH CLAMP CONFIGURATIONS 182 17.4
APPLICATIONS OF THE PATCH CLAMP METHOD 184
18 CELL CYCLE ANALYSIS 187
S. WOELFL, A. KITANOVIC
18.1 ANALYZING THE CELL CYCLE 387 18.2 EXPERIMENTAL ANALYSIS OF THE CELL
CYCLE 189 18.2.1 PREPARING SYNCHRONIZED CELL CULTURES OF S. CEREVISIAE
190 18.2.1.1 CENTRIFUGAL ELUTRIATION 190 18.2.1.2 CELL CYCLE ARREST
USING A-FACTOR 393 18.2.2 IDENTIFICATION OF CELL CYCLE STAGES 191
18.2.2.1 BUDDING INDEX 392 18.2.2.2 FLUORESCENT STAINING OF THE NUCLEUS
192
19 MICROSCOPIC TECHNIQUES 397
S. DIEKMANN
19.1 ELECTRON MICROSCOPY 397 19.1.1 CRYO-ELECTRON MICROSCOPY 199 19.1.2
ELECTRON TOMOGRAPHY 200 19.2 ATOMIC OR SCANNING FORCE MICROSCOPY 200
19.2.1 FORCE SPECTROSCOPY 203 19.2.2 ADVANTAGES AND DISADVANTAGES 203
19.3 LIGHT MICROSCOPY 202
19.3.1 DECONVOLUTION 203 19.3.2 CONFOCAL MICROSCOPY 203 19.3.3 WHY
FLUORESCENCE? 204 19.3.4 NANOSCOPY 204
19.4 MICROSCOPY IN THE LIVING CELL 206 19.4.1 ANALYSIS OF FLUORESCENTLY
LABELED PROTEINS IN VIVO 207 19.4.2 FLUORESCENCE RECOVERY AFTER
PHOTOBLEACHING 208 19.4.3 FLUORESCENCE CORRELATION SPECTROSCOPY 208
19.4.4 FOERSTER RESONANCE ENERGY TRANSFER AND FLUORESCENCE
LIFETIME IMAGING MICROSCOPY 209 19.4.5 SINGLE-MOLECULE FLUORESCENCE 209
20 LASER APPLICATIONS 233
M. VOGEL, R. FINK
20.1 PRINCIPLES OF LASER TECHNOLOGY 233 20.2 PROPERTIES OF LASER
RADIATION 213 20.3 TYPES OF LASERS AND SETUPS 233
20.4 APPLICATIONS 214
20.4.1 LASER SCANNING MICROSCOPY 214 20.4.2 OPTICAL TWEEZERS 215 20.4.3
LASER MICRODISSECTION 215
IMAGE 6
CONTENTS
PART III KEY TOPICS 217
21 CENOMICS AND FUNCTIONAL GENOMICS 239
S. WIEMANN, M. FROHME 21.1 INTRODUCTION 239
21.2 TECHNOLOGICAL DEVELOPMENTS IN DNA SEQUENCING 223 21.3 GENOME
SEQUENCING 222
21.3.1 MAPPING 222
21.3.1.1 RESTRICTION MAPPING AND RESTRICTION FINGERPRINTING 224 21.3.1.2
BAC END SEQUENCING 224 21.3.1.3 GENETIC MAPPING 226 21.3.1.4 RADIATION
HYBRID MAPPING 227 21.3.1.5 HAPPY MAPPING 228 21.3.1.6 MAPPING THROUGH
HYBRIDIZATION 228 21.3.1.7 SEQUENCE TAGGED SITES, EXPRESSED SEQUENCE
TAGS, SINGLE NUCLEOTIDE
POLYMORPHISMS, AND SEQUENCE LENGTH POLYMORPHISMS (AMPLIFIED FRAGMENT
LENGTH POLYMORPHISMS) 231 21.3.1.8 FLUORESCENCE IN SITU HYBRIDIZATION,
FIBER FISH, OPTICAL MAPPING, AND COMPARATIVE GENOME HYBRIDIZATION 232
21.3.2 TIMELINE OF GENOME SEQUENCING 233
21.3.3 GENOME SEQUENCING STRATEGIES 234 21.3.3.1 CONVENTIONAL APPROACH:
RANDOM SHOTGUN STRATEGY 234 21.3.3.2 WHOLE-GENOME SHOTGUN STRATEGY 235
21.3.3.3 SEQUENCING OF THE HUMAN GENOME 237 21.3.4 OUTLOOK FOR GENOME
SEQUENCING 238 21.4 CDNA PROJECTS 238
21.4.1 CDNA LIBRARIES REPRESENT THE CELL S MRNA 238 21.4.2 PRODUCTION OF
CDNA LIBRARIES 240 21.4.3 EST PROJECTS FOR GENE IDENTIFICATION 243
21.4.3.1 WHAT IS AN EST? 243 21.4.4 FULL-LENGTH PROJECTS FOR THE
PRODUCTION OF RESOURCES FOR FUNCTIONAL GENOMICS 245 21.5 FUNCTIONAL
GENOMICS 246
21.6 IDENTIFICATION AND ANALYSIS OF INDIVIDUAL GENES 248 21.6.1
POSITIONAL CLONING 248 21.6.2 GENE TRAP 251
21.6.3 DNA/RNA IN SITU HYBRIDIZATION 253 21.6.4 TISSUE ARRAYS 252 21.7
INVESTIGATION OF TRANSCRIPTIONAL ACTIVITY 253 21.7.1 SERIAL ANALYSIS OF
GENE EXPRESSION 253
21.7.2 SUBTRACTIVE HYBRIDIZATION 254 21.7.3 RNA FINGERPRINTING 257 21.7A
ARRAY-BASED TECHNIQUES 258 21.7.4.1 MACROARRAYS 263
21.7.4.2 MICROARRAYS 262 21.7.4.3 GLOBAL AND SPECIFIC ARRAYS 264 21.7.5
SPECIFICITY AND SENSITIVITY 265 21.8 CELL-BASED METHODS 266
21.8.1 GREEN FLUORESCENCE PROTEIN TECHNIQUES 266 21.8.2 ALTERNATIVES TO
GREEN FLUORESCENCE PROTEIN 267 21.8.3 FLUORESCENCE RESONANCE ENERGY
TRANSFER 268 21.8.4 FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING 269
21.8.5 CELL-BASED ASSAYS 269 21.8.5.1 ASSAY DESIGN 270 21.8.5.2
PIPETTING SYSTEMS 270 21.8.5.3 READING AND RECORDING OF DATA 270
21.8.5.4 DATA ANALYSIS 273
IMAGE 7
CONTENTS I XI
21.9 FUNCTIONAL ANALYSIS OF ENTIRE GENOMES 272
21.9.1 GENOTYPIC SCREENING IN YEAST 272 21.9.2 PHENOTYPIC SCREENING IN
THE MOUSE 273
22 BIOINFORMATICS 275
B. BRORS, K. FELLENBERG 22.1 INTRODUCTION 275
22.2 DATA SOURCES 276
22.2.1 PRIMARY DATABASES: EMBL/GENBANK/DDBJ, PIR, SWISS-PROT 276 22.2.2
GENOME DATABASES: ENSEMBL, GOLDENPATH 276 22.2.3 GENOME DATABASES:
ENSEMBL, GOLDENPATH 277 22.2.4 MOLECULAR STRUCTURE DATABASES: PDB, SCOP
277 22.2.5 TRANSCRIPTOME DATABASES: SAGE, ARRAYEXPRESS, GEO 277 22.2.6
REFERENCE DATABASES: PUBMED, OMIM, GENECARDS 278 22.2.7 PATHWAY
DATABASES AND GENE ONTOLOGY 278 22.3 SEQUENCE ANALYSIS 279
22.3.1 KYTE-DOOLITTLE PLOT, HELICAL WHEEL ANALYSIS, SIGNAL SEQUENCE
ANALYSIS 279 22.3.2 PAIRWISE ALIGNMENT 280 22.3.2.1 LOCAL/GLOBAL 283
22.3.2.2 OPTIMAL/HEURISTIC 283 22.3.3 ALIGNMENT STATISTICS 282 22.3.4
MULTIPLE ALIGNMENT 282 22.4 EVOLUTIONARY BIOINFORMATICS 283 22.4.1
STATISTICAL MODELS OF EVOLUTION 284 22.4.2 RELATION TO SCORE MATRICES
285
22.4.3 PHYLOGENETIC ANALYSIS 285 22.5 GENE PREDICTION 287
22.5.1 NEURAL NETWORKS OR HMMS BASED ON HEXANUCLEOTIDE COMPOSI- TION 287
22.5.2 COMPARISON WITH EXPRESSED SEQUENCE TAGS OR OTHER GENOMES (FUGU,
MOUSE) 288 22.6 BIOINFORMATICS IN TRANSCRIPTOME AND PROTEOME ANALYSIS
288 LL.B.L PREPROCESSING, NORMALIZATION 288 22.6.2 FEATURE SELECTION 290
22.6.3 SIMILARITY MEASURES: EUCLIDEAN DISTANCE, CORRELATION, MANHATTAN
DISTANCE, MAHALANOBIS DISTANCE, ENTROPY MEASURES 290 22.6.4 UNSUPERVISED
LEARNING PROCEDURES: CLUSTERING, PRINCIPAL COMPONENT ANALYSIS,
MULTIDIMENSIONAL SCALING,
CORRESPONDENCE ANALYSIS 291 22.6.5 SUPERVISED LEARNING PROCEDURES:
LINEAR DISCRIMINANT ANALYSIS, DECISION TREES, SUPPORT VECTOR MACHINES,
ANNS 293 22.6.6 ANALYSIS OF OVER-REPRESENTATION OF FUNCTIONAL CATEGORIES
293 22.7 BIOINFORMATIC SOFTWARE 293
23 CELLULAR SYSTEMS BIOLOGY 295
H. SCHMIDT-GIENEWINKEL, S. LEGEWIE, B. BRORS, R. KOENIG 23.1 INTRODUCTION
295
23.2 ANALYSIS OF CELLULAR NETWORKS BY TOP-DOWN APPROACHES 296 23.2.1
MOTIVATION 296 23.2.2 DEFINITIONS AND RECONSTRUCTION OF THE NETWORKS 296
23.2.3 GENE SET ENRICHMENT TESTS 297 23.2.4 NETWORK DESCRIPTORS 298
23.2.4.1 SCALE-FREE NETWORKS 299 23.2.4.2 TRIANGLE MOTIFS IN NETWORKS
299 23.2.4.3 CENTRALITY AND FURTHER TOPOLOGY FEATURES 300
IMAGE 8
CONTENTS
23.2.5 DETECTING ESSENTIAL ENZYMES WITH A MACHINE LEARNING
APPROACH 301
23.2.6 ELEMENTARY FLUX MODES 301 23.2.7 INFERENCE OF REGULATORY
NETWORKS: BOOLEAN AND BAYESIAN NETWORKS 303 23.3 OVERVIEW OF BOTTOM-UP
MODELING OF BIOCHEMICAL NETWORKS 304 23.3.1 MOTIVATION 304 23.3.2
CHOOSING MODEL COMPLEXITY 305 23.3.3 MODEL CONSTRUCTION 305 23.3.4 MODEL
SIMULATION 306
23.3.5 MODEL CALIBRATION 307 23.3.6 MODEL VERIFICATION AND ANALYSIS 309
23.4 BIOLOGICAL EXAMPLES 309
24 PROTEIN-PROTEIN AND PROTEIN-DNA INTERACTION 315 P. UETZ, E. POHL 24.1
PROTEIN-PROTEIN INTERACTIONS 315 24.1.1 CLASSIFICATION AND SPECIFICITY:
PROTEIN DOMAINS 336 24.1.2 PROTEIN NETWORKS AND COMPLEXES 316 24.1.3
STRUCTURAL PROPERTIES OF INTERACTING PROTEINS 318
24.1.4 WHICH FORCES MEDIATE PROTEIN-PROTEIN INTERACTIONS? 319 24.1.4.1
THERMODYNAMICS 339 24.1.4.2 ENERGETICS 320 24.1.5 METHODS TO EXAMINE
PROTEIN-PROTEIN INTERACTIONS 320
24.1.6 REGULATION OF PROTEIN-PROTEIN INTERACTIONS 322 24.1.7 THEORETICAL
PREDICTION OF PROTEIN-PROTEIN INTERACTIONS 323 24.1.7.1 PREDICTING
INTERACTING PROTEINS BY THEIR GENOME SEQUENCE 323 24.1.7.2 PHYLOGENETIC
PROFILES 324
24.1.8 BIOTECHNOLOGICAL AND MEDICAL APPLICATIONS OF PROTEIN-PROTEIN
INTERACTIONS 324 24.2 PROTEIN-DNA INTERACTIONS 324 24.2.1
SEQUENCE-SPECIFIC DNA BINDING 324
24.2.2 THERMODYNAMIC CONSIDERATIONS REGARDING PROTEIN-DNA COMPLEXES 325
24.2.3 METHODS TO STUDY PROTEIN-DNA INTERACTIONS 325 24.2.3.1 STRUCTURAL
CLASSIFICATION OF PROTEIN-DNA COMPLEXES 326
24.2.4 REGULATORY NETWORKS AND SYSTEMS BIOLOGY 327 24.2.4.1 MEDICAL
RELEVANCE OF PROTEIN-DNA INTERACTIONS 328 24.2.5 BIOTECHNOLOGICAL
APPLICATIONS OF PROTEIN-DNA INTERACTIONS 328 24.2.5.1 SYNTHETIC BIOLOGY
328
25 DRUG RESEARCH 331
M. KOEGL, R. TOLLE, U. DEUSCHLE, C. KREMOSER 25.1 INTRODUCTION 331
25.2 ACTIVE COMPOUNDS AND THEIR TARGETS 333 25.2.1 IDENTIFICATION OF
POTENTIAL TARGETS IN THE HUMAN GENOME 332 25.2.2 COMPARATIVE GENOME
ANALYSIS 334 25.2.3 EXPERIMENTAL TARGET IDENTIFICATION: IN VITRO METHODS
334
25.2 A EXPERIMENTAL IDENTIFICATION OF TARGETS: MODEL ORGANISMS 335
25.2.5 EXPERIMENTAL TARGET IDENTIFICATION IN HUMANS 336 25.2.6
DIFFERENCE BETWEEN TARGET CANDIDATES AND GENUINE TARGETS 337 25.2.7
BIOLOGICALS 337
25.2.8 DNA AND RNA IN NEW THERAPEUTIC APPROACHES 339 25.2.9 PATENT
PROTECTION FOR TARGETS 339 25.2.10 COMPOUND LIBRARIES AS A SOURCE OF
DRUG DISCOVERY 340 25.2.11 HIGH-THROUGHPUT SCREENING 341 25.2.12
HIGH-QUALITY PARAMOUNTS IN SCREENING ASSAYS 343
IMAGE 9
CONTENTS XIII
25.2.13 VIRTUAL LIGAND SCREENING 343 25.2.14 ACTIVITY OF DRUGS DESCRIBED
IN TERMS OF EFFICACY AND POTENCY 344 25.2.15 CHEMICAL OPTIMIZATION OF
LEAD STRUCTURES 344 25.3 PRECLINICAL PHARMACOLOGY AND TOXICOLOGY 344
25.4 CLINICAL DEVELOPMENT 346
25.5 CLINICAL TESTING 346
26 DRUG TARGETING AND PRODRUGS 349 G. FRICKER 26.1 DRUG TARGETING 349
26.1.1 PASSIVE TARGETING BY EXPLOITING SPECIAL PHYSIOLOGICAL PROPERTIES
OF THE TARGET TISSUE 350 26.1.2 PHYSICAL TARGETING 350 26.1.3 ACTIVE
TARGETING 351 26.1.4 CELLULAR CARRIER SYSTEMS 354 26.2 PRODRUGS 355
26.2.1 PRODRUGS TO IMPROVE DRUG SOLUBILITY 355 26.2.2 PRODRUGS TO
INCREASE STABILITY 355 26.3 PENETRATION OF DRUGS THROUGH BIOLOGICAL
MEMBRANES 356 26.4 PRODRUGS TO EXTEND DURATION OF EFFECT 357
26.5 PRODRUGS FOR THE TARGETED RELEASE OF A DRUG 357 26.6 PRODRUGS TO
MINIMIZE SIDE EFFECTS 358
27 MOLECULAR DIAGNOSTICS IN MEDICINE 359 S. WOELFL, R. GESSNER 27.1 USES
OF MOLECULAR DIAGNOSTICS 359 27.1.1 INTRODUCTION 359
27.1.2 MONOGENIC AND POLYGENIC DISEASES 359 27.1.3 INDIVIDUAL
VARIABILITY IN THE GENOME: FORENSICS 362 27.1 A INDIVIDUAL VARIABILITY
IN THE GENOME: HLA TYPING 362 27.1.5 INDIVIDUAL VARIABILITY IN THE
GENOME: PHARMACOGENOMICS 362 27.1.6 INDIVIDUAL VARIABILITY IN THE
GENOME: SUSCEPTIBILITY
TO INFECTIOUS DISEASES 363 27.1.7 VIRAL DIAGNOSIS 363 27.1.8 MICROBIAL
DIAGNOSIS AND RESISTANCE DIAGNOSIS 364 27.2 WHICH MOLECULAR VARIATIONS
SHOULD BE DETECTED 364
27.2.1 POINT MUTATIONS 365 27.2.2 INSERTIONS AND DELETIONS 366 27.2.3
NUCLEOTIDE REPEATS 366 27.2.4 DELETION OR DUPLICATION OF GENES 366
27.2.5 RECOMBINATION BETWEEN CHROMOSOMES 366 27.2.6 HEADING3 367
27.3 MOLECULAR DIAGNOSTIC METHODS 367 27.3.1 DNA/RNA PURIFICATION 367
27.3.2 DETERMINATION OF KNOWN SEQUENCE VARIATIONS 368 27.3.2.1 LENGTH
POLYMORPHISM 368 27.3.2.2 RESTRICTION FRAGMENT LENGTH POLYMORPHISM
(RFLP) 368 27.3.2.3 AMPLIFICATION-CREATED RESTRICTION SITES (ACRS) 369
27.3.2.4 AMPLIFICATION REFRACTORY MUTATION SYSTEM (ARMS) 369
27.3.2.5 MUTATIONALLY SEPARATED (MS)-PCR 369 27.3.2.6 ALLELE-SPECIFIC
HYBRIDIZATION 369 27.3.2.7 LIGASE CHAIN REACTION (LCR) 371
27.3.2.8 MINISEQUENCING 373 27.3.2.9 PYROSEQUENCING 371 27.3.2.10
QUANTITATIVE PCR 371 27.3.2.11 CHIP TECHNOLOGY 372
IMAGE 10
XIV I CONTENTS
27.3.2.12 PRODUCTION AND MANUFACTURE OF MICROARRAYS 373
273.2.13 DETERMINATION OF UNKNOWN MUTATIONS 374 27.4 OUTLOOK 375
28 RECOMBINANT ANTIBODIES AND PHAGE DISPLAY 377 S. DUEBEL 28.1
INTRODUCTION 377
28.2 WHY RECOMBINANT ANTIBODIES? 379 28.2.1 RECOMBINANT ANTIBODIES ARE
AVAILABLE IN VITRO WITHOUT IMMUNIZATION 379 28.2.2 ANTIBODIES WITH NEW
CHARACTERISTICS CAN BE CREATED 379 28.3 OBTAINING SPECIFIC RECOMBINANT
ANTIBODIES 379 28.3.1 PREPARATION OF THE VARIETY OF ANTIBODY GENES 380
28.3.2 SELECTION SYSTEMS FOR RECOMBINANT ANTIBODIES 380 28.3.2.1
TRANSGENIC MICE 380 28.3.2.2 IN VITRO SELECTION SYSTEMS 382 28.4
PRODUCTION OF RECOMBINANT ANTIBODIES 384 28.4.1 RECOMBINANT PRODUCTION
SYSTEMS 384 28.4.2 PURIFICATION OF RECOMBINANT ANTIBODIES AND THEIR
FRAGMENTS 385
28.5 FORMATS FOR RECOMBINANT ANTIBODIES 386 28.5.1 MONOSPECIFIC ANTIBODY
FRAGMENTS 386 28.5.1.1 FAB FRAGMENTS 388
28.5.1.2 FV FRAGMENTS 388 28.5.1.3 SINGLE-CHAIN ANTIBODY FRAGMENTS
(SCFV) 388 28.5.1.4 SINGLE-CHAIN FAB FRAGMENTS (SCFAB) 389
28.5.1.5 DISULFIDE-STABILIZED FV FRAGMENTS (DSFV) 389 28.5.1.6 V H AND
CAMEL ANTIBODIES 389 28.5.2 MULTIVALENT ANTIBODY FRAGMENTS 389 28.5.2.1
BIFUNCTIONAL ANTIBODIES 390
28.5.2.2 BISPECIFIC ANTIBODIES 390 28.6 APPLICATIONS OF RECOMBINANT
ANTIBODIES 392 28.6.1 CLINICAL APPLICATIONS 392 28.6.2 APPLICATIONS IN
RESEARCH AND IN VITRO DIAGNOSTICS 392
28.6.2.1 RECOMBINANT ANTIBODIES SELECTED TO AVOID CROSS-REACTIVITY 393
28.6.2.2 INTRACELLULAR ANTIBODIES 394 28.6.2.3 RECOMBINANT ANTIBODIES AS
BINDING MOLECULES FOR ARRAYS 394 28.7 OUTLOOK 394
29 TRANSGENIC AND GENE-TARGETED MICE AND THEIR IMPACT IN MEDICAL
RESEARCH 395 R. SPRENGEL 29.1 OVERVIEW 395
29.2 TRANSGENIC MICE 395
29.2.1 RETROVIRAL INFECTION 396 29.2.2 PRONUCLEAR INJECTION 397 29.3
HOMOLOGOUS RECOMBINATION: KNOCK-OUT (-IN) MICE 398 29.4 CONDITIONALLY
REGULATED GENE EXPRESSION 399
29.5 IMPACT OF GENETICALLY MODIFIED MICE IN BIOMEDICINE 400 29.5.1
ALZHEIMER S DISEASE 403 29.5.2 AMYOTROPHIC LATERAL SCLEROSIS (ALS) 401
29.5.3 PSYCHOLOGICAL DISORDERS 402
29.6 OUTLOOK 402
30 GENE THERAPY. STRATEGIES AND VECTORS 403 A. GROTH, I. HEN 30.1
INTRODUCTION 403
30.2 PRINCIPLES OF SOMATIC GENE THERAPY 404
IMAGE 11
CONTENTS XV
30.3 GERM LINE THERAPY 405
30.4 SETBACKS IN GENE THERAPY 406 30.5 VECTORS FOR GENE THERAPY 406
30.5.1 RETROVIRAL VECTORS 407 30.5.2 ADENOVIRAL VECTORS 430
30.5.3 ADENO-ASSOCIATED VIRUS (AAV) 433 30.5.4 OTHER VIRAL VECTORS 413
30.6 SPECIFIC EXPRESSION 413
31 RNA INTERFERENCE, MODIFIED DNA, PEPTIDE NUCLEIC ACID, AND
APPLICATIONS IN MEDICINE AND BIOTECHNOLOGY 415 N. METZLER-NOLTE, A.
SOSNIAK 31.1 INTRODUCTION 435
31.2 MODIFIED NUCLEIC ACIDS 436 31.2.1 PHOSPHOROTHIOATE 416 31.2.2
METHYLPHOSPHONATE 437 31.2.3 PEPTIDE NUCLEIC ACIDS (PNAS) 438
31.3 INTERACTIONS OF DNA ANALOGS WITH COMPLEMENTARY DNA AND RNA 419
31.3.1 MELTING TEMPERATURE 419 31.3.2 MISMATCH SENSITIVITY 423 31.4 RNAI
423
31.4.1 BIOGENESIS OF SMALL RNAS 422 31.4.1.1 BIOGENESIS OF SIRNAS 422
31.4.1.2 BIOGENESIS OF MIRNAS 422 31.4.2 INCORPORATION INTO RISC 423
31.4.3 POSTTRANSCRIPTIONAL REPRESSION BY MIRNA UND SIRNA 424
31.5 APPLICATIONS 424
31.5.1 ANTISENSE TECHNOLOGY WITH DNA ANALOGS 424 31.5.2 SIRNA IN
BIOTECHNOLOGICAL APPLICATIONS 426 31.5.2.1 DESIGN OF SIRNAS 426 31.5.2.2
NONVECTORIAL APPLICATIONS 427
31.5.2.3 VECTORIAL APPLICATIONS 427 31.5.2.4 OTHER APPLICATIONS FOR PNA
428 31.5.3 COMPARISON OF RNAI WITH DNA ANALOGS FOR ANTISENSE APPLICA-
TIONS 429
32 PLANT BIOTECHNOLOGY 431 H. HILLEBRAND, R. HELL 32.1 INTRODUCTION 431
32.1.1 GREEN GENETIC ENGINEERING - A NEW METHOD TOWARDS TRADITIONAL
GOALS 433 32.1.2 CHALLENGES IN PLANT BIOTECHNOLOGY 432 32.2 GENE
EXPRESSION CONTROL 433
32.3 PRODUCTION OF TRANSGENIC PLANTS 434 32.3.1 TRANSFORMATION SYSTEMS
434 32.3.1.1 AGROBACTERIUM AS A NATURAL TRANSFORMATION SYSTEM 435
32.3.1.2 BIOLISTIC METHOD: GENE GUN 436
32.3.1.3 PLASTID TRANSFORMATION 438 32.3.1.4 VIRAL SYSTEMS 439 32.4
SELECTION OF TRANSFORMED PLANT CELLS 439 32.4.1 REQUIREMENTS FOR AN
OPTIMAL SELECTION MARKER SYSTEM 440
32.4.2 NEGATIVE SELECTION MARKER SYSTEMS 443 32.4.3 POSITIVE SELECTION
MARKER SYSTEMS 442 32.4.4 COUNTER-S ELECTION USING BIFUNCTIONAL MARKER
GENES 443 32.4.5 VISUAL MARKERS 443
IMAGE 12
XVI CONTENTS
32.4.6 SELECTION SYSTEMS, GENETIC ENGINEERING SAFETY, AND MARKER-FREE
PLANTS 443
32.5 REGENERATION OF TRANSGENIC PLANTS 445 32.5.1 REGENERATION
PROCEDURES 445 32.5.2 COMPOSITION OF REGENERATION MEDIA 446 32.6 PLANT
ANALYSIS: IDENTIFICATION AND CHARACTERIZATION
OF GENETICALLY ENGINEERED PLANTS 446 32.6.1 DNA AND RNA VERIFICATION 446
32.6.2 PROTEIN ANALYSIS 448 32.6.3 GENETIC AND MOLECULAR MAPS 448
32.6.4 STABILITY OF TRANSGENIC PLANTS 449
33 BIOCATALYSIS IN THE CHEMICAL INDUSTRY 453 M. BREUER, B. HAUER 33.1
INTRODUCTION 451
33.2 BIOCONVERSION/ENZYMATIC PROCEDURES 454 33.3 DEVELOPMENT OF AN
ENZYME FOR INDUSTRIAL BIOCATALYSIS 456 33.3.1 IDENTIFICATION OF NOVEL
BIOCATALYSTS 456 33.3.2 IMPROVEMENT OF BIOCATALYSTS 458 33.3.3
PRODUCTION OF BIOCATALYSTS 458 33.3.4 OUTLOOK 459
33.3.5 CASE STUDY 1: SCREENING FOR NEW NITRILASES 459 33.3.6 CASE STUDY
2: USE OF KNOWN ENZYMES FOR NEW REACTIONS: LIPASES FOR THE PRODUCTION OF
OPTICALLY ACTIVE AMINES AND ALCOHOLS 460
33.3.7 CASE STUDY 3: ENZYME OPTIMIZATION WITH RATIONAL AND EVOLUTIVE
METHODS 463 33.4 FERMENTATIVE PROCEDURES 462 33.4.1 IMPROVEMENT OF
FERMENTATION PROCESSES 462 33.4.2 CLASSICAL STRAIN OPTIMIZATION 463
33.4.3 METABOLIC ENGINEERING 464 33.4.4 CASE STUDY 4: FERMENTATIVE
PRODUCTION OF N-BUTANOL 465 33.4.5 CASE STUDY 5: PRODUCTION OF GLUTAMIC
ACID WITH C. GLUTAMICUM 466 33.4.5.1 MOLECULAR MECHANISM OF GLUTAMATE
OVERPRODUCTION 467 33.4.6 CASE STUDY 6: PRODUCTION OF LYSINE WITH C.
GLUTAMICUM 468
33.4.6.1 MOLECULAR MECHANISM OF LYSINE BIOSYNTHESIS 468 33.4.6.2
DEREGULATION OF THE KEY ENZYME ASPARTATE KINASE 469 33.4.7 GENOMIC
RESEARCH AND FUNCTIONAL GENOMICS 470 33.4.8 CASE STUDY 7: FERMENTATIVE
PENICILLIN PRODUCTION 470
33.4.9 CASE STUDY 8: VITAMIN B 2 PRODUCTION 471 33.4.9.1 RIBOFLAVIN
BIOSYNTHESIS 473 33.4.9.2 CLASSICAL STRAIN DEVELOPMENT 472
PART IV BIOTECHNOLOGY IN INDUSTRY 473
34 INDUSTRIAL APPLICATION: BIOTECH INDUSTRY, MARKETS, AND OPPORTUNITIES
475 J. SCHUELER 34.1 HISTORICAL OVERVIEW AND DEFINITIONS OF CONCEPTS 475
34.2 AREAS OF INDUSTRIAL APPLICATION OF MOLECULAR BIOTECHNOLOGY 476
34.2.1 RED BIOTECHNOLOGY 477 34.2.1.1 BIOPHARMACEUTICAL DRUG DEVELOPMENT
477 34.2.1.2 DRUG DELIVERY 479 34.2.1.3 CELL AND GENE THERAPY 479
34.2.1.4 TISSUE ENGINEERING/REGENERATIVE MEDICINE 481 34.2.1.5
PHARMACOGENOMICS AND PERSONALIZED MEDICINE 483 34.2.1.6 MOLECULAR
DIAGNOSTIC AGENTS 482
IMAGE 13
CONTENTS XVII
34.2.1.7 SYSTEMS BIOLOGY 483
34.2.2 GREEN BIOTECHNOLOGY 483 34.2.2.1 TRANSGENIC PLANTS 483 34.2.2.2
GENOMIC APPROACHES IN GREEN BIOTECHNOLOGY 484 34.2.2.3 NOVEL FOOD AND
FUNCTIONAL FOOD 484
34.2.2.4 LIVESTOCK BREEDING 484 34.2.3 WHITE AND GRAY BIOTECHNOLOGY 485
34.3 STATUS QUO OF THE BIOTECH INDUSTRY WORLD-WIDE 485
34.3.1 GLOBAL OVERVIEW 485 34.3.2 UNITED STATES 486 34.3.3 EUROPE 486
35 PATENTS IN THE MOLECULAR BIOTECHNOLOGY INDUSTRY: LEGAL AND ETHICAL
ISSUES 487 DAVID B. RESNIK 35.1 PATENT LAW 487
35.1.1 WHAT IS A PATENT? 487
35.1.2 HOW DOES ONE OBTAIN A PATENT? 488 35.1.3 WHAT IS THE PROPER
SUBJECT MATTER FOR A PATENT? 489 35.1.4 TYPES OF PATENTS IN
PHARMACEUTICAL AND MOLECULAR BIOTECHNOLOGY 490
35.1.5 PATENT INFRINGEMENT 490 35.1.6 INTERNATIONAL PATENT LAW 491 35.2
ETHICAL AND POLICY ISSUES IN BIOTECHNOLOGY PATENTS 492 35.2.1 NO PATENTS
ON NATURE 492
35.2.2 THREATS TO HUMAN DIGNITY 493 35.2.3 PROBLEMS WITH ACCESS TO
TECHNOLOGY 494 35.2.4 BENEFIT SHARING 497 35.3 CONCLUSIONS 498
36 DRUG APPROVAL IN THE EUROPEAN UNION AND UNITED STATES 499 G. WALSH
36.1 INTRODUCTION 499
36.2 REGULATION WITHIN THE EUROPEAN UNION 499 36.2.1 EU REGULATORY
FRAMEWORK 499 36.2.2 EMEA 500
36.2.3 NEW DRUG APPROVAL ROUTES 503 36.2.3.1 CENTRALIZED PROCEDURE 502
36.2.3.2 MUTUAL RECOGNITION 503 36.3 REGULATION IN THE UNITED STATES 503
36.3.1 CDER AND CBER 504 36.3.2 APPROVAL PROCEDURE 504 36.4 ADVENT AND
REGULATION OF BIOSIMILARS 506 36.5 INTERNATIONAL REGULATORY
HARMONIZATION 506
37 EMERGENCE OF A BIOTECHNOLOGY INDUSTRY 509 C. KREMOSER
38 THE 101 OF FOUNDING A BIOTECH COMPANY 517 C. KREMOSER 38.1 FIRST
STEPS TOWARDS YOUR OWN COMPANY 537 38.2 EMPLOYEES: RECRUITMENT,
REMUNERATION, PARTICIPATION 522
IMAGE 14
XVIII CONTENTS
39 MARKETING 527
C. KREMOSER
39.1 INTRODUCTION 527
39.2 WHAT TYPES OF DEALS ARE POSSIBLE? 528 39.3 WHAT MILESTONE OR
LICENSE FEES ARE EFFECTIVELY PAID IN A BIOTECH/ PHARMA COOPERATION? 529
39.4 PR AND IR IN BIOTECH COMPANIES 530
APPENDIX 533
FURTHER READING 535
GLOSSARY 553
M. WINK
SUBJECT INDEX 587
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| spelling | An introduction to molecular biotechnology fundamentals, methods, and applications ed. by Michael Wink 2., updated ed. Weinheim Wiley-VCH 2011 XXXIII, 601 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Biotechnologie (DE-588)4069491-4 gnd rswk-swf Molekularbiologie (DE-588)4039983-7 gnd rswk-swf (DE-588)4123623-3 Lehrbuch gnd-content Molekularbiologie (DE-588)4039983-7 s DE-604 Biotechnologie (DE-588)4069491-4 s Wink, Michael 1951- Sonstige (DE-588)124618146 oth DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=021104244&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | An introduction to molecular biotechnology fundamentals, methods, and applications Biotechnologie (DE-588)4069491-4 gnd Molekularbiologie (DE-588)4039983-7 gnd |
| subject_GND | (DE-588)4069491-4 (DE-588)4039983-7 (DE-588)4123623-3 |
| title | An introduction to molecular biotechnology fundamentals, methods, and applications |
| title_auth | An introduction to molecular biotechnology fundamentals, methods, and applications |
| title_exact_search | An introduction to molecular biotechnology fundamentals, methods, and applications |
| title_full | An introduction to molecular biotechnology fundamentals, methods, and applications ed. by Michael Wink |
| title_fullStr | An introduction to molecular biotechnology fundamentals, methods, and applications ed. by Michael Wink |
| title_full_unstemmed | An introduction to molecular biotechnology fundamentals, methods, and applications ed. by Michael Wink |
| title_short | An introduction to molecular biotechnology |
| title_sort | an introduction to molecular biotechnology fundamentals methods and applications |
| title_sub | fundamentals, methods, and applications |
| topic | Biotechnologie (DE-588)4069491-4 gnd Molekularbiologie (DE-588)4039983-7 gnd |
| topic_facet | Biotechnologie Molekularbiologie Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=021104244&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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