[CELLMOL]

• Robert Hooke (1665) observed compartments in cork, under a microscope, and first named cells (the basic unit of biology)
• Antoine van Leeuwenhoek, a few years later, produced better lenses that magnify up to 300x
• Early progress in cell was slow due to limited microscope resolutions and the descriptive nature of cell biology
• By the 1830s, compound microscopes were used (two lenses) which increased magnification and resolution, allowing structures 1 micrometer in size to be seen
• Robert Brown identified the nucleus, a structure inside plant cells, using a compound microscope
• Matthias Schleiden concluded all plant tissues are composed of cells, and Theodor Schwann made the same conclusion for animals
• Cell theory


  All organisms consist of one or more cells, the cell is the basic unit of structure for all organisms, all cells only arise from preexisting cells
• Three historical strands of cell biology

  • Cytology (cellular structure and optical techniques)
  • Biochemistry (cellular function)
  • Genetics (information flow and heredity)
• Cytology is the oldest strand, starting with Hooke and Leeuwenhoek
• Genetics is the more modern strand, identifying smaller cell components like genes and DNA
• Biochemistry has formulated techniques to study what happens inside cells, how they communicate, their components, and why they function
• Cytology


  • Deals with cellular structure and observation using optical techniques
• Light microscope


  Allowed identification of organelles within cells
• Microtome


  Cuts specimens into thin slices for microscope preparation
• Dyes


  Help differentiate cells in a specimen
• Limit of resolution


  How far apart objects must be to appear as distinct
• Brightfield microscopy


  White light passes through a specimen to illuminate
• Fixing, staining, embedding


  Preparations that may distort tissues
• Phase contrast/differential interference contrast microscopy


  • Exploit differences in the phase of light passing through a structure with a refractive index different than the surrounding medium
• Fluorescence microscopy


  • Detects fluorescent dyes or labels to show locations of substances in the cell
• Confocal scanning


  • Uses a laser beam to illuminate a single plane of fluorescently labeled specimens
• Electron microscope


  • Uses a beam of electrons rather than light, with a much higher magnification and resolution than light microscopes
• Transmission electron microscopy (TEM)


  Electrons are transmitted through the specimen
• Scanning electron microscopy (SEM)


  The surface of a specimen is scanned, by detecting electrons deflected from the outer surface
• Biochemistry dates from the work of Fredrich Wöhler (1828), who showed that a compound made in a living organism could be synthesized in the lab
• Louis Pasteur (1860s) showed that yeasts could ferment sugar into alcohol, and the Buchners (1987) showed that yeast extracts could do the same, leading to the discovery of enzymes
• The Embden-Meyerhof pathway and the Krebs cycle were described in the 1920s and 1930s, important in cellular energy metabolism
• Important advances in biochemistry

  • Radioactive isotopes
  • Subcellular fractionation
  • Ultracentrifuges
  • Chromatography
  • Electrophoresis
  • Mass spectrometry
• Gregor Mendel's experiments with peas (1866) laid the foundation for understanding the passage of hereditary factors from parents to offspring
• Walther Flemming (1880) saw threadlike bodies in the nucleus called chromosomes, and Wilhem Roux (1883) and August Weisman suggested that chromosomes carried the genetic material
• Morgan, Bridges, and Sturtevent (1920s) were able to connect specific traits to specific chromosomes in the fruit fly Drosophila melanogaster
• Friedrick Miescher (1869) first isolated DNA, which was known to be a component of chromosomes by 1914 and composed of 4 different nucleotides by the 1930s
• Experiments in the 1940s began to implicate DNA as the genetic material, and Watson and Crick proposed the double helix model for DNA structure in 1953
• Important techniques in genetics

  • Ultracentrifugation and electrophoresis
  • Nucleic acids hybridization
  • Recombinant technology
  • DNA sequencing
  • Bioinformatics
  • Yeast two-hybrid system
  • Nanotechnology
• Scientific method


  Formulate a hypothesis, collect and interpret data, accept or reject the hypothesis
• Research approaches in cell biology

  • In vitro (using purified chemicals and cellular components)
  • In vivo (using live cells or organisms)
  • In silico (using computer analysis of large data)
• Different live organisms or cells are usually used as models in cell biology experiments
• "Facts" are tenuous and dynamic
• Dynamic


  There is always something that we can debunk
• The scientific method


  1. Formulate hypothesis

  2. Collect and interpret data

  3. Accept or reject model/hypothesis