Bio 150 Introduction to Molecular Cell Biology
Miriam De Vera, PhD
Lecture 1.1 Cell Biology Timeline
Molecular Cell Biology (Modern Cell Biology)
- A deductive science => to understand the whole, you have
to study the parts
- Whole = the cell itself
- Parts = organelles inside the cell (including the
extracellular environment)
- Includes molecular aspect
- 3 fields of origination (oldest to youngest):
1. Cytology study of the ultrastructure (or
structure) of the cell; microscopy (use of
magnifying equipment)
2. Biochemistry
3. Genetics
- The fields mentioned develop as independent
disciplines, but in time, they have certain overlaps
In studying the structure of the cell (Cytology),
you will need to have information on how
chemical processes (Biochemistry) and
propagation of cells (Genetics) take place
The Cell Biology Timeline
(Refer to diagram on last page)
- At first the 3 threads are separate, but as it reaches
the 20th century, the 3 threads intertwine to form
the cord leading to the field of cell biology.
In chronological order starting from 1600s to 21st century:
Field Significant Event
C *Started with the invention of microscopy
*Robert Hooke coined the word cell from the
latin cellula; utilized cork slices and found that
they are made of compartments or groups and
referred each of them as cellula or cell
*Only cork cell walls were seen by Hooke
C *Anton van Leeuwenhoek more complex
microscope; observed motile living microscopic
organisms; 1st to describe his observations to
the Royal Society of London although there are
also other members of the guild of lensmakers
*Development of lenses that are used for the
study of very small organisms
C *Brown Brownian movement, described
nuclei; better resolution able to describe
ultrastructure (unlike Leeuwenhoek who only
observed movements due to low resolution
lenses)
B *Wohler synthesizes urea in the lab.
*Urea organic material produced by animals
*The fact that he was able to synthesize urea
outside living things suggests that the process
of the formation of organic materials need not
occur within a living thing.
*Chemical processes which will result in organic
molecules can occur outside living things
*Whatever processes occur outside to produce
urea are the same processes occurring inside
the living organism (human body)
*Living processes follow universal, physical, and
chemical laws BIO + CHEM
C Cell Theory
*Schleiden: The basic unit of plant life is the cell
*Schwann: The basic unit of animal life is the
cell
*If you are alive, you should be made of cells
C *Virchow evolution of cells; every cell comes
from preexisting cells
C *Kolliker described mitochondria in muscle
cells
*Implication of discovery of diff. organelles
resolution of lens systems used for observing
cells are becoming better
*Observed mitochondria without stains! Wow!
C *Devt. of dyes and stains (acidophilic, basophilic,
neutral) helps in dissolving many parts
B *Pasteurization
*Pasteur links living organisms to specific
processes inverse of what Wohler said
(processes in living things follow physical and
chem laws)
*There are certain processes occurring in nature
that are attributed to living things.
*Example: Fermentation (Pasteur). Leave milk
ferment due to activities of microorganisms
*Theres a connection between the presence of
organisms with how certain materials undergo
degradation or anabolic processes
G *Mendel Father of Genetics; use of pea plts.
*Genetics youngest, rel. new; 2 decades after
Darwin published Origin of Species
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G *Miescher discovers DNA (isolated from pus;
might be from the bacteria)
*DNA another biomolecule found in living
tissues bc around the time of Mendel, nucleic
acids were not yet well known (only C, L, P)
*implication of DNA is not yet certain
C *Invention of the microtome
*no specific person to which is it attributed.
Theres a guild of people making diff kinds of
microtome
*Implication: more microscopic slices for better
observation of cells/tissues
C&G *Fleming identifies chromosomes
*Chromosome (genetics) 1 parent cell can
give rise to 2 daughter cells; transmission of
parental material to offspring in mitotic division
*Chromosome (cytology) structure; better
resolution
C&G *Roux and Weissman chromosomes carry
genetic information (conjecture only)
*chromosomes are relatively constant in
mitosis (from parent to daughter)
C *Golgi complex described
*implication: further improvement of the
resolution of microscopes
B *Buchner and Buchner fermentation by cell
extracts (unlike Pasteur who used whole
bacteria)
*You dont need intact cells (whole bacteria) to
demonstrate fermentation. You just need to get
an extract from the bacteria
*There are very specific chem. processes within
living things that can trigger certain metabolic
processes
G *Correns, von Tschermak, de Vries
rediscovery of Mendels laws
*2 Mendelian basic laws: Segregation and
Independent Assortment
*They found out na inunahan na pala sila ni
Mendel
C&G *Chromosomal theory of heredity (implied from
Roux and Weissman)
*Importance of chromosomes - contain factors
C&G *Feulgen - stain for DNA; darkly pronounced
DNA due to acid hydrolysis
G *Morgan and colleagues develop genetics of
Drosophila
B *Embden and Meyerhof describe the glycolytic
pathway
*Glycolysis common starting process for both
aerobic and anaerobic metabolism
*You need to know how cells stay alive. How do
they get energy?
G *Levene postulates DNA as a repeating
tetranucleotide structure
*DNA primary NA material associated with
chrom (thats why more focused on DNA)
B *Svedberg discovery of ultracentrifuge; a
means of separating cell extracts of different
sedimentation rates
*Svedberg unit greater number higher
sedimentation rate faster to settle
therefore that material has more mass
B *Krebs TCA cycle (extension of glycolytic
pathway)
C *Knoll and Ruska invention of the electron
microscope; use of electrons instead of light to
look at microscopic structures
C&B *Claude isolates mitochondrial fractions
*Biochem: isolation of organelles using
ultracentrifuge
*Cytology: mitochondria = cell structure
G *Avery, McLeod, McCarty DNA as agent of
genetic transformation
*based on Griffiths expt: Pneumococcal bacterial
strains R (rough avirulent) and S (smooth
virulent)
*R strain no infection
*S strain with infection
*kill S strain the inoculate no infection
*Mix dead S strain with live R strain w/
infection (nonvirulent transformed to become
virulent)
*Transforming agent came from dead S strain
*Avery, et al repeated this experiment
*Protein from the live virulent strain inoculate
no transformation.
*DNA from virulent strain inoculate w/
transformation
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 *If there are agents (enzymes) that are included
in the inoculum that deactivates the DNA no
transformation
G *Alfred Hershey and Martha Chase establish
DNA as the genetic material
*confirmatory expt
*they worked with bacteriophages (protein coat
with NA inside). Proteins and DNA were
radiolabeled using sulfur and phosphorus.
*Sulfur binds to proteins. Phosphorus binds to
DNA.
*In the bacteria, only the phosphorus-labeled
nucleic acid entered while sulfur-labeled
proteins were left outside.
*DNA enters and multiplies inside the bacteria
(how viruses replicate)
B&G *Watson and Crick proposed double helix for
DNA
*Rosalind Franklin died already so no nobel
prize
C *Palade, Sjostrand, Porter developed
techniques for electron microscopy
*1950s post WW2 so there are many scientific
discoveries and devt of techniques for study
G(B) *Kornberg DNA polymerase for addition of
bases to DNA
G *Genetic code elucidated.
*For every codon has a corresponding AA that will
be translated to functional proteins (not all codons
are expressive)
B *Berg, Boyer, Cohen DNA cloning techniques
or DNA Recombinant Technology
*in vitro studies combining the DNA from
different materials and replicating them
G *DNA sequencing methods
B *Heuser, Reese, and colleagues deep-etching
techniques (cell observation techniques)
*Etching sculpting the outlines of image;
sculpting ultrastructure of cells
*involves making out the surface of the interior
to make specimen visible in EM
*Biochem: bc of chemicals and processes
needed to make that shape to be viewed in EM
*Using materials to make a model or a cast of a cell
= Cast is a 3d to be observed under an electron
microscope
*Deep-etching meaning you will first cut the cell by
freezing it then the surface inside will be used for
casting
*Not the cell surface but the structure inside it
C *Allen and Inoue (Asian) perfect video-enhanced
contrast light microscopy
*software-related, digital
*to video them while they are still alive and has
higher resolution
B&G *1st transgenic animals produced fish,
amphibians
*animals that might have a gene from
plants/animals/bacteria
C *Green Fluorescent Protein (GFP) used to
detect functional proteins in living cells; protein
that is fluorescent in the dark; came from
organisms which feature bioluminescence
jellyfish (Aequorea victoria)
*Functional proteins intact, newly synthesized
post-translated protein; where GFP attaches
*visual elucidation
G *Dolly the sheep cloned
C *Stereoelectron microscopy used for 3-D
imaging; better resolution that stereomicrosce
B *Human genome sequenced 2001-2005
(Human Genome Project)
B *Mass spectrometry used to study proteomes
*Proteomics study of proteins, sequences of
proteins
*Proteome => set/collection of proteins
expressed by an aggregate or a cluster of genes
which are quietly related
*Prions = misfolded proteins that leads to loss
of function. They are able to affect properly-
folded proteins hence causing spongiform
encephalitis.
G *Bioinformatics genomics (and proteomics);
to analyze sequence data
B *Yeast two-hybrid systems used to analyze
protein-protein interactions
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 *Yeast used in the study of many genetic and
mitotic processes since they are more similar to
eukaryotes (compared to using bacteria)

*easier to study and you can infer more about

eukaryotic systems
C *Fluorescence resonance energy transfer
(FRET) microscopy - used to study molecular
interactions
G *Quantum dots - used to improved fluorescent
imaging

*the discipline has been developing even before

2000s Quantum Biology application of
quantum physics in the study of biological
systems

*Quantum physics feature some predictability;

basic quantum mechanics can help predict how
molecular processes can proceed within cells

*Molecular processes occurring within cells

consist of subatomic particles

*behavior of subatomic particles follows

quantum laws
C *Advanced light microscopy - begin to surpass
the theoretical limit of resolution
G *Nanotechnology - allows rapid sequencing of
entire genomes to become routine; 1000x
smaller than the microscale

*21st century 3 fields highly intertwined

*First exam will include microscopic techniques
(fluorescence microscopy)
*Assignment: Continue diagram until year 2015 (hard copy)

But I trust in Your unfailing love. I will rejoice because You

have rescued me. - Psalm 13:5

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