exe 1

• Early Schools of Thought:

  • Vitalism: Intact cells possess a "vital force" and studying life requires looking into intact cells
  • Mechanism: To study life, cells must be dissected like a machine
• Two Roots of Molecular Biology:

  • Biochemistry: Focuses on the structure and properties of biomolecules
  • Microbial Genetics: Provides information on the genetic material, its transmission, and expression, using simple systems like phages and bacteria
• Molecular Biology:

  • Defined by William T. Astbury in 1945 as the study of the physical and chemical structure of biological macromolecules
  • Present-day definition: The study of genes and their products, and how these products function and interact in the organization and perpetuation of living things
• The Scope of Molecular Biology:

  • Genetic Material:
  • Identity
  • Replication
  • Reading stored information
  • Regulation of gene expression
  • Biomolecules:
  • Synthesis
  • Degradation
  • Transport in and out of the cell
  • Cellular structure and functions:
  • Supramolecular/ultracellular structures
  • Functions of specialized cells
  • Molecular Basis of Biological Phenomena:
  • Aging
  • Development
  • Immune response
  • Diseases and their treatment
• Approaches to problems:

  1. Correlation of structure and function:

  • Examples:
  • Collagen (tendon protein): Triple helix provides additional strength in structural functions
  • DNA: Double-stranded with specific base pairing for stability and replicability
  • Cell membrane: Non-polar fatty acid chains prevent free passing of polar substances

  2. Physical measurements:

  • Ultracentrifugation
  • Electrophoresis
  • Infrared Absorption spectroscopy

  3. In vitro approach:

  • Using crude and reconstituted extracts
• The Logic of Molecular Biology:

  • Efficiency:
  • During evolution, competition and survival became determinants of efficiency
  • Little energy and material are wasted, e.g., gene expression and regulation
  • Development and Evaluation of Models:
  • Models are tentative explanations of how a system works, tested for validity, and revised/re-designed to fit new experimental evidence
  • Strong Inferences:
  • All possible explanations for a particular phenomenon are stated and experimentally eliminated one by one until only one remains - strong inference
• The Transforming Principle:

  • Frederick Griffith (1928) conducted a transformation experiment on Diplococcus pneumoniae (Pneumococcus)
  • Griffith's Experiment showed that information from heat-killed S-type bacteria was transferred to live R-type bacteria, resurrecting the S-type
  • In vitro Transformation by M.H. Dawson and J.L. Alloway confirmed the transforming principle/agent responsible for the transformation
• Chemical Nature of the Transforming Substance:

  • Ostwald T. Avery, Colin M. MacLeod, and Maclin McCarty (1944) identified DNA as the transforming substance through various isolation steps and qualitative chemical tests
  • Elementary Chemical Tests showed DNA as the transforming principle with specific properties and reactions
• The Blender Experiment:

  • Alfred Hershey and Martha Chase (1952) experiment established that DNA is the genetic material, not the protein, using labeled phages
  • Structural Studies on DNA by various researchers like Pheobus Levene, Erwin Chargaff, Linus Pauling, Maurice Wilkins, and Rosalind Franklin contributed to understanding the DNA double helix structure revealed by James Watson and Francis Crick in 1953