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


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 Drs. DiResta  and  Mallery
             Spring and Fall Semesters
 Text: Essential Cell Biology, 5th Edition  
       by Alberts et al,  Publisher: Norton Publishing, 2020
          Student Resources for ECB - book options.   a fact about books
    Some Web Resources:
             American Society Cell Biology Web Seminarstake-a-look
          &  Journal of Molecular & Cellular Biochemistry  

   Additional resourse links which may be useful in future classes:
               The Virtual Library of Biochemistry & Cell Biology (special topics)
              Access  Excellence - a national biology education resource of the
             National Health Museum & originally sponsored by Genetech,
                AE Student Resources,   AE graphics Gallery,   Scitable,
             Virtual Cell animations  
              

 

 

 

 

 

 

 

                                                                                                                          C1... pages 1-36
Fundamentals of CMB...
 
     The goal of cell & molecular biology is to understand the molecular basis of cell function
     and the fundamental cellular processes ranging from cell respiration to cell division.
 
           EXPERIMENTAL APPROACHES used in studying CMB are multidisciplinary & include:
              biochemical & biophysical experimentation; molecular & genetic manipulation
              of cellular functions at the molecular, cellular and organismal levels.              
          CMB's primary procedural approach has been a REDUCTIONIST approach…                  
              a definitive methodological approach of 20th century science =      GRIND & FIND*.  
              i.e., breaking apart a cell into all its individual parts and molecules.
     
     REDUCTIONISM suggests "knowing the parts may explain the function of the whole."
                it is also a bottoms-up approach: "one can't truly understand what one can't build." 
        next    What's missing in a Reductionist Approach to CMB?*          [cartoon]                    


     

 

 

       

 

 

 

 

 

  
    Thus Life is more than inanimate individual molecules,      Life is COMPLEXITY... 

    Modern day CMB must account for Complexity and how Complex Systems act.

    Complexity: is where a system has so many parts that the system...
 
         1.  may interact in many different ways*, so that the whole takes on a realm of its own
         2.  can adapt and evolve to changing conditions
         3.  is prone to sudden and seemingly unpredictable changes
         4.  its collective characteristics cannot easily be predicted from its sole components
         5.  so that the WHOLE IS GREATER than and often significantly different than
                                the SUM of its PARTS...    Life exhibits EMERGENT PROPERTIES.

     A new level of emphasis in CMB has been SYNTHETIC BIOLOGY with one goal being:
              Can we construct a living cell 'off the shelf' if we know ALL its molecular parts ???
                     "What I cannot create, I do not understand."   Richard Feynman (1988)  
 
               but, we must begin our study of Life and the Cell somewhere so let's undertake
               a look at the individual components making up a Complex System of a Cell & Life.

  
 

 

 

 

     

 

 

 

 

 

    


  CMB is rooted in the 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, 
                  which enhances a gene pool's reproductive fitness, 
                  leading to progressively better adaptation via Natural Selection
     u          these principles can lead to morphological change via natural selection* are
               applied repeatedly over millions of cell generations, & are basis of evolution.

 
   

 

 

 
 
 
 
 
 
 

 

 

 

 
 2. Cell Theory...  "All living things are made of Cells",
        "a cell is a small, membrane bounded compartment, filled with concentrated aqueous solution
         of reactive chemicals... a collection of catalysts that, acting as a group, causing complex series
        of chemical reactions, which end up replicating all of the catalysts in the set, and that divides
        into two sets, & the process repeats with each daughter set ".
                       "A living cell is a magic puzzle box full of elaborate and changing molecules".  
                                                                 Delbruck (1949) - a father of molecular biology and 1969 Nobel Laurate.       
 emoji 1839 - Early proponents of a Cell Theory were...  
                                      Matthias Jakob Schleiden (1822-1881) - pic   &  Theodor Schwann (1810-1882) - pic
          1855 - pathologist Rudolf Virchow posed a maxim "Omnis cellula e cellula"...
                                                                  that every cell arises from another cell.
         1863 ►Charles Darwin (1809-1882)... hypothesizes that "probably all the origins beings which
                                       have ever lived on this Earth have descended from some primordial form
                                       into which life was first breathed".  
                                              i.e., cells living today can trace their ancestry back to ancient times...
                                                     so there must be a common ancestral cell.
                      LUCA*  =  Last Universal Common Ancestor
                           is the hypothesis that all organisms on Earth have descended from a
                           common ancestor... a common ancestral cell  or  gene pool,  selected for its better
                                   fitness through the processes of evolution,  via mechanisms of Natural Selection.
                                            
            premise:  LUCA is a single cell that lived perhaps 3-4 billion yrs ago from which ALL LIFE has since evolved.
                                                

                            
 

 

 

 

 

 

  

Consequences of Cell Theory:

 Cell Theory replaces Vitalism which was a mainstream scientific thought of 18-19th century,
            Vitalism was the school of scientific thought, that attempted to explain the nature of life 
            as resulting from a  "vital force", peculiar only to living organisms and different 
            from all other physical forces found outside living things; but Cell Theory prompted...
      
'Mechanists' - believed life was a mechanical process, a theory that all natural phenomena
            can be explained entirely by LAWS of CHEMISTRY & PHYSICS without a "vital force".
  

  
      a modern interpretation:
             "There are no laws of Chemistry or Physics unique only to the Living Condition."
   
               from the Cell Theory we see that the CELL is FUNDAMENTAL UNIT of ALL LIFE...
                       and though MAN & MOUSE* have very different anatomical structures,
                       their cells & organelles are basically the same, and on a letter-for-letter
                       basis about 80-85% of human genes have counterparts in the mouse...
  
►  thus studying cells in one organism has direct application to other organisms.

    

 

 

 

     

  

 

TheTree of Life & Cell Typing
 phylogeny tree of life    (refer to chapter 1)
 CELLULAR ORGANISMS have been grouped together by a binomial taxonomic system
     such as...   Kingdoms* based upon morphology... (descriptions & pic 1st by Carl Linnaeus)
    
  however, CMB using a molecular approach has added to our taxonomic pattern...  
  
                 today we have a higher order than Kingdom...     3 DOMAINS* NAS-8
                            EUBACTERIA      -     true bacteria
                            ARCHAEA           -     ancient prokaryotes        
                            EUKARYA            -     modern eukaryotes

  Carl Woese, (7/15/1928-12/30/12 pdf ) knew ribosomes & rRNA are found in all cells.  Thus, 
   if all cells are derived from a common ancestor[NAS-1], then their nucleotide sequence changes
   over time may indicate divergence (loss of relatedness) through phylogeny (family trees).

    Woese compared nucleotide sequences of the small* rRNA subunit* from many species...
       protocol*:  By comparing similar & divergent sequences, this new  RNA phylogeny tree
                         produced a tree with only 3 distinct branches or Domains   (ecb fig 9.23*)   
      Table*:      of some key differences between ARCHAEA, BACTERIA, & EUKARYOTES 
 

  Genome sequencing indicates that many organisms contain genes from many sources,
         ...including VIRUSES,  ...maybe there should be a 4th Domain - Origin of Viruses. 

 

 

 

 

 

 

 

 
another way of distinguishing cells has been...    STRUCTURAL CELL TYPING.    

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

     E'douard Chatton (FR biologist) in 1925 was 1st to characterize differences between
          prokaryote & eukaryote systems of cell organization.
                                  Chatton, E. 1925. Ann. Sci. Nat. Zool. 10e serie, 1-84.

1.  PROKARYOTE - "pro" = before + "karyon"Gk-kernel (or nucleus)... includes archaea bacteria and   
          today's eubacteria, including cyanobacteria (blue green algae)...  [pic*];
          includes members of the original Kingdom Monera (now 2 Domains Archaea & Eubacteria),
          are microscopic single-celled organisms, often lacking membrane-bound organelles. 

   Characteristics:   [√often defined by differences to the other cell plan]  
          3 main cell shapes in prokaryotic cells:  cocci, bacilli, spirochetes*
          genes contain "naked DNA" -, i.e., DNA with no proteins - chromosomes?*
         they lack significant internal membrane bound organelles
         have a little internal compartmentation  fig 1.2a* vs. a eukaryotic cell
        typing can be via differential Gram Staining* of bacterial cell wall
         sizes - 0.1 to 10 µm diameter  (100nm to 10,000nm = 5 to 500 ribosomes)
              largest bacteria discovered*   		 

 

     

 

 

 

 

 

 

 
 
 
 
 
 

 

 
2. EUKARYOTIC:   [eu -true   karyon -nucleus...]   cell plan of multi-cellular organisms...
         eukarya:   includes the algae & protozoa, fungi & slime molds, & all plants & animals,
                          [ i.e., 4 of the 5 Kingdoms : Protista, Fungi, Plantae, & Animalia ]
    
    Common CHARACTERISTIC of EUKARYOTES: 
  
          nucleus - 'may have been single greatest step in evolution of higher life forms '
              genes - in "chromosomes*"... colored bodies made of DNA + histone proteins    
                               karyotypes  &  chromosome locales*  &  chromosome activity via locale*
                                 contain much more DNA (1,000x  more) than prokaryotes.   
          extensive internal membranes - endomembrane system* (nuclear memb + ER + Golgi + vesicles)
           presence of more flexible "walls = ecm*" (allows endocytosis/phagocytosis)
          presence of organelles- significant internal compartmentalization of function
                             ORGANELLE - a subcell part that has a distinct metabolic function
                                 ecb/4e Panel 1-2a: schematic drawings of animal &  plant 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
                                                                                                                    

 

 
 
 
 

 

 

 

 
the Universal Characteristics of all Cells:  
               (helps provide circumstantial evidence for a "LUCA*" ?)
   
1.  all cells store their hereditary information in DNA...  DNA
   
2.  all cells replicate hereditary info via same mechanism... templated polymerization*
          templated replication                templated transcription      
3.  all cells transcribe hereditary info into an RNA via templated transcription*
   
4.  all cells translate RNA by same mechanism via codon:anticodon "Chargaff " pairing
     using the same universal "GENETIC CODE "

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

 G :  C 

    next page next  

 
 
   

    


5.  all cells use protein catalysts (enzymes) to make/break covalent bonds
                               E  +   S    <--->    ES    <--->   E  +   P

6.  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 in a
          process known as, differential gene activity (in a time dependent fashion).    
 
7.  "A crucial fact of Life is that it has ability to push chemistry away from Equilibrium".
          all cells metabolize- using free energy to stay far away from chemical equilibrium.
          Consumption of free energy creates covalent bonds (which resist the disordering
          effects of thermal motion), as specified by hereditary info in a DNA sequence.
                 The processes* that cells have evolved to obtain free energy include:
                        heterotrophy - oxidation of foods (via oxidation of covalent bonds)
                        lithotrophy - chemical electron donors provide energy (H2, H2S, S, Fe)
                        autotrophy - capture of light energy via pigments (photosynthesis)
            N2 & CO2 are stable and unreactive & reduction to NH2 & CH2O needs energy.
               
8.  all cells are enclosed in a spontaneously aggregating amphiphilic phospholipid bilayer.
           membranes  regulate nutrient/water transfer & concentrate molecules internally.
                       Advantages of hydrophobic bilayers in cells & in membranes*
              
       --> go to model organisms        
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 

 
 

 



                                                      

 

 

 

 

 





















    IGNORE ALL MATERIAL BELOW THIS POINT IN THE CLASS PRESENTATION

 

 

 

     On Dec. 3, 1967 Dr. Christian Bernard - of  Cape Town, South Africa,
     using techniques pioneered at Stanford University
     by Drs. Norman Shumway and Richard Lower,
     performed the first successful
     heart transplant at Groote Schuur Hospital."

     The patient, Louis Washkansky, lived 18 days and died of a lung infection.

           back

 


n  
n   What types of cells does CMB study ?
 
     Molecular Life seems to occur at succeeding level of complexity:

         1.  Biochemical  (as in viruses) ...                          DNA  -->  RNA  -->  Protein   [polymers]

         2.  CELLULAR  (as single celled organisms)...     bacteria, protozoa, HeLa cells, etc

         3.  Multicellular aggregations ...                             organs & organisms (plants & animals) 
 
         4.  Entities ...                                                          Humans - spirit, creativity, consciousness
                                                                                                                                                  
► Model Organisms*    cheap, plentiful, prolific reproducers, with simple genomes
                                      & unique properties for practical research analysis:    [see pg 26 -35]*
   
                            CMB's research model organisms have often been used to study gene expression:
                                    Bacteriophages - a virus that infects bacteria; today used as cloning vectors
                                    Escheriichia coli - bacteria common to the human colon; molecular work horse  [Ecoli database]
                            Eukaryotic models include:
                                    primitive eukaryotic anaerobic protozoan cell with 2 nuclei - [ Giardia - Giardiasis ]
                                single cells - Saccharomyces cerevisiae - yeast                   [ pic ]
                                    plants - mustard plants Arabidopsis thaliana                         [ pic ]
                                    nematode - Caenorhabditis elegans                                      [ pic ]
                                    animals - fruit fly - Drosophilia melangaster
                                                  -  Zebrafish* - Danio rerio                                      [ pic ]             
                                                  -  Mus musculus [Mickey] - common house mouse  &  its genome
            
► additional model systems for genetic & embryonic development research... cells grown in the lab.
                         Hela cells*  [cells - filopodia*] - an immortal cell line of human cervical cancer cells
                                                   that grew prolifically in culture (George & Margaret Gey at JHU)
                         fibroblast cells* - connective tissue cells easily grown in tissue culture
                          immortal stem cells       (Stem Cell Journal   -   Stem Cell fraud)
      
   next lecture                                                                                                                                              































a)   Please ignore the links shown below this point...
 
   
                some references:  Voyage of the H.M.S. Beagle    &    a Snoppy cartoon.

                  some other concepts:   Early ideas on Origins of the Cell Theory

                
         Major historical landmarks in Cell Structure (ecb Table 1.1 pg24)*



& Some cell links   



             
9.  a summary of Top 10 Properties of Cells* (Life)