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
GENENTECH, Inc.
    
    AE STUDENT RESOURCES  AE graphics Gallery
     Mallery's CMB RESOURCES  &  Journal of Visualized Experimentstake-a-look*.

 

 

 

 

 
                                                                                                                  C1... pages 1-30

Description...

 
        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 experimentation 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 "
                              can we construct a living cell 'off the shelf' from its molecular parts

 

 

 

 

 

 

 
Foundations of Modern Cell & Molecular Biology
...
       dates from
1944 to 2009 - dawn of the modern Molecular Cell Biology age
                                             
&   is the stuff of Biology 255
                                    
includes the integration of molecular structure & cell function...
                                         NHGRI Dynamic History Timeline  &  NHGRI Timeline Landmarks graphic
    
      some personal relevance...
       my mother (nee 1906): saw advent of auto, airplane, radio, T.V., man on the moon...
          me (1943): heart transplants (where was 1st ?), rise of antibiotics, Rover & Phoenix on Mars,
                         DNA & transgenic animals,  artificial genes & manipulation, cloning, human genome...
  
        
CMB is part of our modern popular culture -
Movies: Jurassic Park &  Species-I*   Movie-III
                  & is part of highest recognition in science?   Nobel Prize in Medicine & Chemistry
  

                          to reiterate...    The aim of Modern CMB is to interpret the
                                                 properties of life & organisms through the
                                 
 
              structure of their constituent cellular molecules.
 

 

 

 

 

 

 

 


 
   CMB gave us... the    Central Dogma of molecular biology
                                                                                 DNA --> RNA --> Protein                              mcb fig 4.1*
  

 
                                        "Life begets Life " - is now seen at the molecular level,
                                                                       
 as the faithful replication of DNA...
   
 
  CMB asks... what do all cells have in common...
             the answer   =  "their molecules & chemical reactivity"
                                        their
biochemistry: proteins, lipids, carbs are all the same...
                                        we need to understand
Molecular Biology to see how life works
  
 
   CMB is about energy & reactivity, movement & change, action & reaction;
                                      
 
almost everything that happens in life. happens in cells...
                                        
which likely boils down to
ENZYME CATALYSIS.

   CMB replaces the gross anatomy and physiological studies of the 17th & 18th century,
                                   with the biology of molecules &
molecular systems
in  21st century.
  

   
       but as Erwin Chargaff  (former Chair of Bioc @ Columbia U; pic  Heineken Prize winner) has said,
                                 
" CMB...   is the practice of Biochemistry without a license "  
   
  
end1

 

 

 

 

 

 

 

 

 

    
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 the environment and habitat
             enhances a 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 & Darwin's books & publications  +  Snoppy cartoon  
 
   

 

 

 

 

 

 

 

 
 
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* = single cell that lived perhaps 3-4 billions yrs 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 18th 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 only 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
NAS-8
                    EUBACTERIA     -    
true bacteria
                    ARCHAEA           -    
ancient prokaryotes         [ Kingdoms pic & 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 - "pro" = before + "karyon" = nucleus...     includes archaea bacteria  &
                today's prokaryotes also include  blue green algae,  bacteria,  &  eubacteria-fig 1.1b
                includes members of the original Kingdom monera, now Kingdoms Archaea & Bacteria.

               they lack significant 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 algae & protozoa, fungi & slime molds, & all plants & animals.
                                    [ 4 Kingdoms of Protista, Fungi, Plantae, & Animalia ]

    
        7 common CHARACTERISTIC of EUKARYOTES: 
  

          nucleus - 'may have been single greatest step in evolution of higher animals'
                      genes in "chromosomes
*"...   colored bodies... made of DNA + protein  [karyotype*]
                      contains more DNA (1,000x  more) than prokaryotes   
          extensive internal membranes - endomembrane system
* (nuclear memb + ER + Golgi + vesicles)
          presence of organelles- significant internal compartmentalization of function
                              organelle - a subcell part that has a distinct metabolic function
          presence of flexible cell walls (allows endocytosis/phagocytosis*) 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

 

 

 

 

 

 

 
Universal Characteristics of Cells   (& thus all Life)

   
1.  all cells store their hereditary information in DNA
  

2.  all cells replicate their hereditary info via templated polymerization*
          templated replication                templated transcription      
  

3.  all cells transcribe hereditary info into intermediate RNA via templated transcription
*
  
4.  all cells translate RNA in same mechanistic way via codon:anticodon "Chargaff" pairing

                
5'  AUG  3' - mRNA
3'  UAC  5'
- tRNA 
                     
-met 
chargaff pairing A  :  T   or   A  :  U

G  :  C 

 
 







5.  all cells regulate rate of gene transcription/translation, so only a portion of full
         repertoire of possible RNA's/proteins are copied, thus hereditary info dictates
         not only nature of cell's proteins, but also when/where they are to be made via
         so called, differential gene activity.
 6.  all cells use protein catalysts (enzymes) to make/break covalent bonds

                                      E  +  
S    <--->    ES    <--->   E  +   P
 7.  all cells metabolize - consume free energy and are far from chemical equilibrium.
     Consumption of free energy creates covalent bonds (which resist the disordering
     effects of thermal motion), thereby creating hereditary info in a DNA sequence.
                       The processes that cells have evolved to obtain free energy include:
                                heterotrophy - oxidation of foods (covalent bonds)
                                lithotrophy - chemical electron donors provide energy
                                autotrophy - capture of light energy via pigments (photosynthesis)
             
N2 & CO2 are stable and unreactive & reduction to NH2 & CH2O uses energy.
8.  all cells are enclosed in a spontaneously aggregating amphiphilic phospholipid bilayer:
     membranes regulate nutrient/water transfer, concentrate molecules internally,
     all membrane have embedded protein transport molecules            
 
 a text description of the PROPERTIES of  LIVING CELLS* read this
 
                                         Top 10 Properties of Cells*(Life)              milestones in CMB

 

 

 

 

 

 

 

 

 

What cells types will we be looking at? [review of Prokaryote, Eukaryote, & Virus]
        
                                                                                                                                    
µ Model Organisms*   cheap, plentiful, prolific reproducers, with simple genomes
       & unique properties for practical research analysis:                           [see pg 25 - 28]*
   

     
cell & molecular biology's research model organisms have included:
              Bacteriophages - a virus that infects bacteria; today used as cloning vectors
         
    Escheriichia coli - bacteria common to the human colon; molecular work horse    [database] 
              Giardia -  a primitive eukaryotic cell, an anaerobic protozoan cell with 2 nuclei [Giardiasis]
                         other eukaryotic models include:
                     
             single celled -  Saccharomyces cerevisiae - yeast     [ pic ]
       
                           plants - mustard plants Arabidopsis  thaliana          [ pic ]
    
                               nematode - Caenorhabditis elegans                          [ 2002 Nobel ]
                             
     animals - fruit fly Drosophilia melangaster
                                       
[Mickey] mouse - Mus
musculus - common house mouse  &  its genome
            
     
additional model systems for genetic & embryonic development research... cells grown in the lab.
                         
Hela cells*   [pic + pic*] - an immortal cell line (George & Margaret
Gey at JHU)
                               
fibroblast cells      (connective tissue cells easily grown in tissue culture)
   next lecture        immortal stem cells       (Stem Cell Journal   -   Stem Cell fraud)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

n  
n