Bil 255 - Cell and Molecular Biology...
                   structure, function, & the molecules of cells

 Professors  Glaser  and  Mallery
 Spring and Fall Semesters
   text: Molecular Cell Biology, 6h Edition  
           by Lodish et al,  Publisher: W.H.Freeman, NY, 2007

 Web Resources: American Society Cell Biology Web Seminarstake-a-look
The Virtual Library of Biochemistry & Cell Biology (special topics)   &
        Access  Excellence - a national biology education resource of the
                National Health Museum & originally sponsored by
     AE STUDENT RESOURCES  AE graphics Gallery*
          Mallery's  web-links  for CMB RESOURCES.





                                                                                                                  C1... pages 1-30

        The goal of cell & molecular biology is to understand the molecular basis of cell function and the fundamental cellular processes ranging from cell division and protein trafficking to signal transduction and cell migration, to the formation of tissues during development and wound healing. The experimental approaches used in studying cell regulation and function are multidisciplinary and include: biochemical and biophysical approaches and molecular and genetic manipulation of functions at both the cellular and organismal levels.
               CMB uses a REDUCTIONIST philosophy…
                        the definitive methodological approach of 20th century science.

      REDUCTIONISMg* is a fundamental research protocol of CMB
        i.e., " knowing the parts may explain the function of the whole "
                              a bottoms-up approach - " one can't truly understand what one can't build "





CMB is rooted in the 2 major theories of Biology
    1. Evolution  - Darwinian Natural Selection.
u       changes in the allele frequency of a population's gene pool 
       from one generation to another generation… 
             as influenced by a habitat, 
             which enhances population's reproductive fitness, 
             & leading to progressively better adaptation via  Natural Selection
     u          these principles of morphological change and natural*selection
               applied repeatedly over millions of cell generations, are basis of evolution

                          Voyage of H.M.S Beagle     Snoppy cartoon  + Darwin's books & publications








2. Cell Theory...
"All living things are made of cells"...
          'small, membrane bounded compartments, filled with 
           concentrated aqueous solutions of reactive chemicals'
                µ " All organisms on Earth have a common descent from a LUCA,
a common ancestral cell  or gene pool, selected for its better fitness
                        through the processes of evolution,  via mechanisms of Natural Selection. "
          LUCA = a single cell that lived perhaps 3-4 billions years ago & from which ALL LIFE has since evolved.

                two main proponents of Cell Theory were...  
Schleiden- pic*  &  Schwann- pic*

                                               Some historical landmarks in cell structure*

                                    other resources:   Early ideas on Origins of the Cell Theory & Some cell links




 Consequences of Cell Theory:
 Cell Theory replaces Vitalism*...  which was the mainstream scientific thought of 17th century,
            Vitalism was the school of scientific thought, that attempted to explain the nature of life 
as resulting from a vital force,
"a soul", peculiar to living organisms and different 
                         from all other physical forces found outside living things.
            Mechanists believed that life is essentially a mechanical process, that can be explained
                          entirely by the workings of laws of chemistry and physics without a vital force’.       
                                          VITALISM                    vs.                MECHANICALISM
                                    living                         vs.                    non-living
                                              organic                     vs.                    non-organic              

                                              Vital Force               vs.                    no vital force

       "There are no laws of Chemistry or Physics unique to the living condition. "
                       The cell is the fundamental unit of all life, and though MAN & MOUSE have
                        very different anatomical structure, their cells & organelles are the same,
                        and on a letter-for-letter basis 85% of their genes are the same, thus
                        studying cells in one organism has direct application to other organisms.




Cell Types & The Tree of Life phylogeny tree of life              (refer to chapter 1)
   All living CELLULAR ORGANISMS may be grouped into...    3 DOMAINS
                    EUBACTERIA     -    
true bacteria
                    ARCHAEA           -    
ancient prokaryotes         [ picture  collage ]
                    EUKARYOTA      -    
modern eukaryotes

   Carl Woese,   (an interview compared the nucleotide sequence of the single small-unit  rRNA*
       from many species...     rRNA is found in all cells and therefore,
if all cells are derived form a common progenitor[NAS-1], their sequence changes
over time can indicate divergence (loss of relatedness) through phylogeny (family trees)

        The RNA phylogeny tree produced, by comparing similar & divergent sequences,
a tree with 3 distinct branches (Domains)   (mcb fig 1.3*)






   but within the 3 domains there are only 2 successful Plans of Cellular Organization
distinguished primarily by size & the type of internal structures (the organelles) they possess:

    1.  PROKARYOTE - "before nucleus"     [includes archaea bacteria*]  &                     
                today's prokaryotes also include  blue green algae,  bacteria*,  &  eubacteria-fig 1.1b*

               they lack membrane bound organelles              
               genes contain "naked DNA" -, i.e., there are no "chromosomes?"
               little to no internal compartmentation   fig 1.2a*   +     E.coli*
                             size range - 0.1 to 10 µm diameter
              3 primary cellular shape in prokaryotic cells
                           - cocci, bacilli, spirochetes*
EM of bacteria






    2.  EUKARYOTIC   [eu -true   karyon -nucleus...]   cell plan of multi-cellular organisms
                        eukarya: includes the fungi, algae, protozoa, slime molds, & all plants & animals.

         7 common CHARACTERISTIC of EUCARYOTES: 

            nucleus - 'single greatest step in evolution of higher animals'
                      genes in "chromosomes
*"...   colored bodies... made of DNA + protein  [a karyotype]
                      contains more DNA (1,000x  more) than procaryotes   
            extensive internal membranes - endomembrane system
            presence of organelles- significant internal compartmentalization of function
                              organelle - a subcell part that has a distinct metabolic function
            presence of flexible cell walls (allows phagocytosis/endocytosis*) especially in animal cells
            presence of cytoskeleton
*  (provides framework to be larger & provide form/shape)
            reproduce sexually
            usually larger   - cell volume 10X > than bacteria  - size 5.0 to 20 µm diameter
mcb6e  fig 9.1: schematic drawings of animal*plant* cells






  Some Basic Properties of Cells & thus Life...    or     How Cells Work
  • cells have an evolutionary origin - all cells are derived from other cells...
             originally from a single primordial cell [LUCA some 3 bya]
    Chemical Evolution
  • cells: highly complex mix of biomolecules (C, O, H, N) ---> cellular structural complexity
             show structural complexity - review [ figure 9.5a pg 376 (mcb)] 
                                                                  [ animal* & plant* cells  (fig 9.1 pg 373 - mcb)]
             cells come in 2 fundamental types - prokaryote & eukaryote 
    (read pgs 1-4: mcb6e)*   
  • cells obey laws of chemistry & physics (the laws of Universe)
    cells build and degrade numerous molecules, generally via use of ATP   fig 1.14*
    cells extract energy from environment and maintain a homeostasis far from equilibrium
             cells acquire and utilize energy -via metabolic pathways: Glycolysis,  Krebs,  ETC  
             cells metabolize - are capable of 1,000's of reactions (via ENZYME-protein pathways)
             cells are capable of self regulation - series of ordered reactions that are self-adjusted
             cells divide, grow, & differentiate leading to cell Form & Function
    cells osmoregulate - control what gets in/out of membranes*  (organelle or plasma)




  Basic Properties of Cells & thus Life...    continued
  • cells are motile...   cells are involved in numerous mechanical activities assembly, disassembly,
             movement of organelles, motor proteins - all via the cytoskeleton  fig 1.15* + webinar
             vesicle & organelle walking*

  • cells respond to stimuli - via external surface or internal cell receptors  fig 1.16*
  • cells grow and divide...
             cells use nucleic acids for genetic information
     cells are capable of self-replication
       -   MitosisMeiosis - fig 1.17*             

             cells regulate their gene expression (RNA and protein synthesis)

  • cells die  - absence of life is a most defining characteristic of living  
    apoptosis - programmed cell death due to absence of certain growth signals - fig 1.19*
                               via cysteine-aspartic acid proteases

                                                    Top 10 Properties of Cells* (Life)
              next - milestones



















 a refresher on Cell Organelles

  Top 10 Properties of Cells*

 a refresher on Cell Organelles

  Historical Landmarks in the  Cell Theory -    historical landmarks in cell structure*

1665  Robert Hooke  publishes Micrographia
Royal Society
 minute chambers called cells... were walls of plant cells (bark)
1680  Leeuwenhoek publishes Animacules  magnifying lens, microscopes,  & pond water
1697  Redi negates
Spontaneous Generation  
 all life arises from pre-existing life  [??? - controls]
1809 Jean Baptiste Lamarck  " Living body is a mass of cells "
1824 Henri Dutrouchet  mild acid dissolves extra-cellular matrix  some of 1st biochem.
1833 Robert Brown  describes nucleus of orchid cells
1838 Mathais Schleiden (plants) & 1839 
Theodor Schwann  (animals)
 tissues are made of cells  =  Cell Theory
- the formal birth of discipline of "
Cell Biology"
1858 Rudolf Virchow " Every animal appears as sum total of vital units, 
  each of which bears the complete characteristics of life

      ...suggests cells are formed from pre-existing cells.
1879 Walther Flemming  first detailed description of cell division, mitosis & chromosome
1912 Jacques Loeb    removes sea urchin eggs: chemically induces embryo development
n                     Some links to Encyclopedia Britannica (accessible on UM campus- offsite needs a license)  


SKIP The material below....

1951-81: Birth of Modern CMB… continued   (mostly genomic sciences)

Linus Pauling (1951) [osu] alpha helix-beta sheet - right handed, 3.6 aa/turn (0.54nm)

Photograph 51

 Maurice Wilkens [NZ Bio   Rosalin Franklin - Xray diffraction
                      3.4mu,  0.34nm,  2.0 nm      (Voyager   & its  golden record)
 Watson & Crick (1953)  Nature 171: 737-738   &   964-967 (1953).
   "A Structure for deoxyribonucleic acid”                          The Discovery of the Structure of DNA
   "General implications of structure of deoxyribonucleic acid"      
 Joe Hin Tjo (1955) defines 46 as the exact number of human chromosomes
 Max Perutz & John Kendrew (1957) - 1st 3D  structure of a protein myoglobin
 Fred Sanger ('58- Nobel for molecular structure INSULIN - made by beta cells of islets of Langerhans;
                          protein of 2 chains [
alpha chain
(21 aa) & beta chain (30 aa)], linked by sulfur atoms.
- Nobel for helping to determine Nucleic Acid sequences (dideoxy methodology)  
 1961  Holley, Khorana, Nirenberg decipher the Genetic Code -5'-UUU-3' = N-phe-C
          S.Brenner, F.Jacob, & M. Meselson discover mRNA
 1962   Peter Mitchell - cell respiration & energy transduction - chemiosmosis hypothesis & ETC.


1955  Arthur Kornberg discovers DNA Polymerase

1958  Meselson and Stahl describe semi-conservative replication of DNA
1961  Holley, Khorana, Nirenberg decipher the Genetic Code -5'-UUU-3' = N-phe-C
       S. Brenner, F. Jacob, & M. Meselson discover mRNA
1962  Peter Mitchell - cell respiration & energy transduction -chemiosmosis hypothesis
1962 first restriction endonuclease enzymes described by several groups [biotechnology]
1972 Stanley Cohen & Herbert Boyer first recombinant DNA plasmids
1975  Gunter Blobel - signal transduction hypothesis
1977  Phillip Sharp & Richard Roberts - Split genes introns/exons; splicing
1978  Tom Cech & Sidney Altman - catalytic RNA     RIBOZYMES  
1981  Transgenic animals and fruit flies become the geneticist's lab rat


Early Historical Milestones in CMB... 
                       Between 1860-1920's  two new areas of biology evolve into CMB…
       what's important is concept of what was done (CELL FREE EXTRACTIONS), not specifically what they did.
                                                 Do NOT memorize names and dates
... isolation & chemical characterization cell substances...                             
            1828  Freiderich Wohler synthesizes 1st natural biological product in lab... from urine & oxalic acid from spinach UREA                   
1838  Gerhardus Mulder isolates free of cell... fibrous, acid precipitate  = protein
1869  Friedrich Miescher isolates
an acidic material (nuclein) from from nuclei of white blood cells & sperm of Salmon
            1897  Eduard Buchner
cell free yeast extracts that convert glucose  --> alcohol
          1900's H. Emil Fischer define structural makeup of cellular molecules peptide bond...  16 of 22 amino acid discovered
 2. Genetics...  
study of inheritance/characters in plants & animals...  
1865  G. Mendel
 [Mendel Web] dominant/recessive; dihybrid crosses; true value was his quantitative approach to science
1900  Carl CORRENS, Hugo DeVIRES, Ernst TSCHERMAK Mendel's work rediscovered by 3 independent geneticists
Walter SUTTON & Theodor BOVERI chromosomal theory of inheritance  (significance - realized Meiosis matches Mendel)
         1902  Archibold GARROD founder"biochemical genetics" alkaptonuria -1st suggestion: mutations = defective proteins = disease
            1909  Wilhelm JOHANNSEN coins term GENE (mendelian unit) & concepts phenotype & genotype

1911-1920's  T.H.Morgan (paper) &  Alfred Sturtevant  & Calvin Bridges    Drosophilia -  chromosome linkage & mapping, etc. 

  1925 to 1965 - Cell & Molecular Biology comes of age...
Period of discovery of chemical nature of gene &  merging of disciplines
biochemistry & genetics into
MOLECULAR GENETICS   Do NOT memorize names & dates
           1928  Fred Griffith - demonstrates "transforming" principle (agent causes pneumonia)
1930  George Beadle - drosophila white eye mutant is due to defective gene = dysfunctional enzyme = mutation
           1941  G.Beadle  &   E. Tatum - coin the concept...      "one gene   =   one enzyme"   
           1944  Avery, MacLeod & McCarty - open the modern era of molecular genetics
                          - proteases don't alter gene transformation,
but DNAses inactivate transformation, thus DNA is genetic material.
                            1st use of enzymes to test for active biological activity & products - becomes the 'in vogue' experiments of the "era"
Barbara McClintock - jumping genes (transposons)
Erwin Chargaff - shows amounts of bases A = T and G = C
           1952  Alfred Hershey
  biography & Martha Chase - experiment uses 32P & establish DNA as genetic material in viral  infection
  1950-90 -    Birth of Modern CMB and Structural Biology... 
                NHGRI Timeline Landmarks pic       NHGRI Dynamic History Timeline
 ...A Brief History of Biotechnology           Do NOT memorize names and dates