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The Search for the Structure of Life: A History of Molecular Biology provides the historical knowledge behind techniques founded in molecular biology as well as an appreciation of how and by whom these discoveries were made. It deals with the evolution of intellectual concepts in the context of active research, in approachable language for readers with a variety of backgrounds. Each chapter is preceded by a prologue and ends with an epilogue to create continuity and put the contents of individual chapters within the complete framework of molecular biology. This foundational work also functions as a historical and conceptual supplement to many related courses in biochemistry, biology, chemistry, genetics, and history of science. It demonstrates how the roots of discovery and advances – and an individual’s own research – have grown out of the history of the field, presenting a more complete understanding and context for scientific discovery.
Expands on the development of molecular biology from the convergence of two independent disciplines of biochemistry and genetics
Discusses the value of molecular biology in a variety of applications, as well as research ethics and societal implications of research
Emphasizes the human aspects of research and the consequences of such advances to society
Researchers, academics, and students in life sciences, for example in molecular biology, evolutionary biology, biochemistry, genetics/molecular genetics, epidemiology, oncology, gerontology, cell biology, and microbiology, as well as many disciplines beyond biological science; secondarily, as an auxiliary text for specific courses and seminars at colleges and universities
CHAPTER 1 BEGINNINGS
? Some ancient intuitions
? Spontaneous generation
? The demise of vitalism
? The rise of modern biology
? The microscope opens a new world
CHAPTER 2 THE ORIGINS OF BIOCHEMISTRY
? Recognition of proteins
? Some proteins are catalysts: Enzymes
? What enzymes do, and why it is so important
? How do enzymes work?
? Proteins fulfill many roles
? What are proteins made of?
CHAPTER 3 THE CHEMICAL STRUCTURE OF PROTEINS
? The peptide hypothesis
? Colloid or macromolecule?
? Some unexpected results
? Proteins as homogeneous polypeptides
? Fred Sanger and the sequence of insulin
Box.3.1 Separation Methods
Box 3.2 Immunological methods
CHAPTER 4 PROTEINS IN THREE DIMENSIONS
? The first globular protein structures
Box 4.1 How to Determine Protein Structure
A. The principle of diffraction
B. Diffraction from fibers
C. Diffraction from crystals
CHAPTER 5 THE ORIGINS OF GENETICS
? Classical genetics and the rules of trait inheritance
? Friar Gregor Mendel plants some peas
? Mendel formulates the two laws of inheritance
? Mendel’s laws have extensions and exceptions
? Mendel was long ignored
? Darwin, Mendelism, and mutations
? Genes are arranged linearly on chromosomes and can be mapped
? What do genes do, and what are they made of?
CHAPTER 6 NUCLEIC ACIDS
? Miescher's mysteries
? The chemical structures of nucleic acids
? “What is life?”
? DNA carries genetic information
? Mysterious numbers
Box 6.1 Gel electrophoresis
CHAPTER 7 THE GREAT SYNTHESIS
? Bacteria and viruses have genetics, too: the introduction of cloning
? Critical experiments show that the genetic material is DNA
? Revealing DNA structure; perspiration plus inspiration
? "It has not escaped our attention..."
? The most beautiful experiment
? DNA sequence and protein sequence; a tale of two languages
? Methods Box: Reading a helix and chasing replication
CHAPTER 8 HOW DNA IS REPLICATED
? What is the mode of replication?
? How does replication proceed?
? The lagging strand problem
CHAPTER 9 THE CENTRAL DOGMA
? Speaking in different languages
? Intuiting a dogma
? Who is the Messenger?
? The great decade: 1952-1962
CHAPTER 10 THE GENETIC CODE
? How might a code function?
? What kind of code?
? What were the code words?
? The code
CHAPTER 11 GENE TO PROTEIN: THE WHOLE PATH
? What was known in 1960?
? The rest of the story
? Regulation of transcription in bacteria
CHAPTER 12 EUKARYOTES POSE NEW PROBLEMS
? What is a eukaryote?
? The origin of eukaryotes
? The three domains of life
? Interrupted messages and splicing
? Every cell type has special needs and functions
? Multiple levels of control
? Chromatin and nucleosomes
? Too much DNA? Junk DNA?
CHAPTER 13 DIFFERENTIATION AND DEVELOPMENT
? Two Ideas about development dominated thinking in ancient times
? The Introduction of scientific approaches to the field of development
? An opportunity missed?
? What do we know about development and differentiation at present?
? Embryonic stem cells (ESC) serve as a model for pluripotency
? The Molecular Basis of Differentiation and Development
• The maternal-zygotic transition
• Genes control development: the case for the fruit fly
? Nuclear transfer experiments and the principle of genetic equivalence
? Genome reprogramming towards earlier phases of development is possible
CHAPTER 14 RECOMBINANT DNA: THE NEXT REVOLUTION
? The power of DNA recombination
? How to clone DNA
? Construction of recombinant DNA molecules needs restriction endonucleases and ligases
? The first recombinant DNA molecules
? Polymerase chain reaction and site-directed mutagenesis
? Manipulating the genetic content of eukaryotic organisms
? CRISPR, the gene-editing technology of today and tomorrow
Box 12.1: Cloning vectors. The expression of recombinant genes.
CHAPTER 15 UNDERSTANDING WHOLE GENOMES: CREATING NEW PARADIGMS
? The evolution of sequencing methodology
? Genomic libraries contain the entire genome of an organism as a collection of recombinant DNA molecules
? There are two classic approaches for sequencing large genomes
? Ultrafast sequencing allows deep analysis of genomes
? Whole genomes
? The human genome project
? ENCODE results raise question. Whence biology?
? So, what was learned from ENCODE?
? Transcription factors interact in a huge network
? Where is ENCODE leading?
? Attempts at a contemporary definition of a gene
Box 15.1 The classic definition of a gene is not consistent with recent observations
CHAPTER 16 WHOLE GENOMES AND EVOLUTION
? Evolutionary theory: from Darwin to the present day
? Classifying organisms: Phylogenetics
? Phylogenetics goes molecular
? The comparative genomics revolution
? Tracing human evolution
CHAPTER 17 PRACTICAL APPLICATIONS OF RECOMBINANT DNA TECHNOLOGIES
? Catching criminals and freeing the innocent
? Production of pharmaceutical compounds in recombinant bacteria or yeast
? Genetic engineering of plants
? Gene therapy
? A CRISPR revolution?
? Cloning of whole animals
? Jurassic park or de-extinction