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Bio 150 Introduction to Molecular Cell Biology B *Wohler synthesizes urea in the lab.

Miriam De Vera, PhD


Lecture 1.1 Cell Biology Timeline *Urea organic material produced by animals

Molecular Cell Biology (Modern Cell Biology) *The fact that he was able to synthesize urea
- A deductive science => to understand the whole, you have outside living things suggests that the process
to study the parts of the formation of organic materials need not
- Whole = the cell itself occur within a living thing.
- Parts = organelles inside the cell (including the
extracellular environment) *Chemical processes which will result in organic
- Includes molecular aspect molecules can occur outside living things
- 3 fields of origination (oldest to youngest):
1. Cytology study of the ultrastructure (or *Whatever processes occur outside to produce
structure) of the cell; microscopy (use of urea are the same processes occurring inside
magnifying equipment) the living organism (human body)
2. Biochemistry
3. Genetics *Living processes follow universal, physical, and
- The fields mentioned develop as independent chemical laws BIO + CHEM
disciplines, but in time, they have certain overlaps C Cell Theory
*Schleiden: The basic unit of plant life is the cell
In studying the structure of the cell (Cytology),
*Schwann: The basic unit of animal life is the
you will need to have information on how
cell
chemical processes (Biochemistry) and
*If you are alive, you should be made of cells
propagation of cells (Genetics) take place
C *Virchow evolution of cells; every cell comes
from preexisting cells
The Cell Biology Timeline C *Kolliker described mitochondria in muscle
(Refer to diagram on last page) cells
- At first the 3 threads are separate, but as it reaches
the 20th century, the 3 threads intertwine to form *Implication of discovery of diff. organelles
the cord leading to the field of cell biology. resolution of lens systems used for observing
cells are becoming better
In chronological order starting from 1600s to 21st century:
Field Significant Event *Observed mitochondria without stains! Wow!
C *Started with the invention of microscopy C *Devt. of dyes and stains (acidophilic, basophilic,
neutral) helps in dissolving many parts
*Robert Hooke coined the word cell from the
B *Pasteurization
latin cellula; utilized cork slices and found that
they are made of compartments or groups and
*Pasteur links living organisms to specific
referred each of them as cellula or cell
processes inverse of what Wohler said
(processes in living things follow physical and
*Only cork cell walls were seen by Hooke
chem laws)
C *Anton van Leeuwenhoek more complex
microscope; observed motile living microscopic *There are certain processes occurring in nature
organisms; 1st to describe his observations to that are attributed to living things.
the Royal Society of London although there are
also other members of the guild of lensmakers *Example: Fermentation (Pasteur). Leave milk
ferment due to activities of microorganisms
*Development of lenses that are used for the
study of very small organisms *Theres a connection between the presence of
C *Brown Brownian movement, described organisms with how certain materials undergo
nuclei; better resolution able to describe degradation or anabolic processes
ultrastructure (unlike Leeuwenhoek who only G *Mendel Father of Genetics; use of pea plts.
observed movements due to low resolution *Genetics youngest, rel. new; 2 decades after
lenses) Darwin published Origin of Species

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G *Miescher discovers DNA (isolated from pus; C&G *Feulgen - stain for DNA; darkly pronounced
might be from the bacteria) DNA due to acid hydrolysis
G *Morgan and colleagues develop genetics of
*DNA another biomolecule found in living Drosophila
tissues bc around the time of Mendel, nucleic B *Embden and Meyerhof describe the glycolytic
acids were not yet well known (only C, L, P) pathway

*implication of DNA is not yet certain *Glycolysis common starting process for both
C *Invention of the microtome aerobic and anaerobic metabolism

*no specific person to which is it attributed. *You need to know how cells stay alive. How do
Theres a guild of people making diff kinds of they get energy?
microtome G *Levene postulates DNA as a repeating
tetranucleotide structure
*Implication: more microscopic slices for better
observation of cells/tissues *DNA primary NA material associated with
C&G *Fleming identifies chromosomes chrom (thats why more focused on DNA)
B *Svedberg discovery of ultracentrifuge; a
*Chromosome (genetics) 1 parent cell can means of separating cell extracts of different
give rise to 2 daughter cells; transmission of sedimentation rates
parental material to offspring in mitotic division
*Svedberg unit greater number higher
*Chromosome (cytology) structure; better sedimentation rate faster to settle
resolution therefore that material has more mass
C&G *Roux and Weissman chromosomes carry B *Krebs TCA cycle (extension of glycolytic
genetic information (conjecture only) pathway)
C *Knoll and Ruska invention of the electron
*chromosomes are relatively constant in microscope; use of electrons instead of light to
mitosis (from parent to daughter) look at microscopic structures
C *Golgi complex described C&B *Claude isolates mitochondrial fractions
*implication: further improvement of the
resolution of microscopes *Biochem: isolation of organelles using
B *Buchner and Buchner fermentation by cell ultracentrifuge
extracts (unlike Pasteur who used whole
bacteria) *Cytology: mitochondria = cell structure
G *Avery, McLeod, McCarty DNA as agent of
*You dont need intact cells (whole bacteria) to genetic transformation
demonstrate fermentation. You just need to get
an extract from the bacteria *based on Griffiths expt: Pneumococcal bacterial
strains R (rough avirulent) and S (smooth
*There are very specific chem. processes within virulent)
living things that can trigger certain metabolic *R strain no infection
processes *S strain with infection
G *Correns, von Tschermak, de Vries *kill S strain the inoculate no infection
rediscovery of Mendels laws *Mix dead S strain with live R strain w/
infection (nonvirulent transformed to become
*2 Mendelian basic laws: Segregation and virulent)
Independent Assortment *Transforming agent came from dead S strain

*They found out na inunahan na pala sila ni *Avery, et al repeated this experiment
Mendel *Protein from the live virulent strain inoculate
C&G *Chromosomal theory of heredity (implied from no transformation.
Roux and Weissman) *DNA from virulent strain inoculate w/
*Importance of chromosomes - contain factors transformation

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*If there are agents (enzymes) that are included *Using materials to make a model or a cast of a cell
in the inoculum that deactivates the DNA no = Cast is a 3d to be observed under an electron
transformation microscope
G *Alfred Hershey and Martha Chase establish
DNA as the genetic material *Deep-etching meaning you will first cut the cell by
freezing it then the surface inside will be used for
*confirmatory expt casting

*they worked with bacteriophages (protein coat *Not the cell surface but the structure inside it
with NA inside). Proteins and DNA were C *Allen and Inoue (Asian) perfect video-enhanced
radiolabeled using sulfur and phosphorus. contrast light microscopy

*Sulfur binds to proteins. Phosphorus binds to *software-related, digital


DNA.
*to video them while they are still alive and has
*In the bacteria, only the phosphorus-labeled higher resolution
nucleic acid entered while sulfur-labeled B&G *1st transgenic animals produced fish,
proteins were left outside. amphibians

*DNA enters and multiplies inside the bacteria *animals that might have a gene from
(how viruses replicate) plants/animals/bacteria
B&G *Watson and Crick proposed double helix for C *Green Fluorescent Protein (GFP) used to
DNA detect functional proteins in living cells; protein
that is fluorescent in the dark; came from
*Rosalind Franklin died already so no nobel organisms which feature bioluminescence
prize jellyfish (Aequorea victoria)
C *Palade, Sjostrand, Porter developed
techniques for electron microscopy *Functional proteins intact, newly synthesized
post-translated protein; where GFP attaches
*1950s post WW2 so there are many scientific
discoveries and devt of techniques for study *visual elucidation
G(B) *Kornberg DNA polymerase for addition of G *Dolly the sheep cloned
bases to DNA C *Stereoelectron microscopy used for 3-D
G *Genetic code elucidated. imaging; better resolution that stereomicrosce
B *Human genome sequenced 2001-2005
*For every codon has a corresponding AA that will (Human Genome Project)
be translated to functional proteins (not all codons B *Mass spectrometry used to study proteomes
are expressive)
B *Berg, Boyer, Cohen DNA cloning techniques *Proteomics study of proteins, sequences of
or DNA Recombinant Technology proteins
*in vitro studies combining the DNA from
different materials and replicating them *Proteome => set/collection of proteins
G *DNA sequencing methods expressed by an aggregate or a cluster of genes
B *Heuser, Reese, and colleagues deep-etching which are quietly related
techniques (cell observation techniques)
*Prions = misfolded proteins that leads to loss
*Etching sculpting the outlines of image; of function. They are able to affect properly-
sculpting ultrastructure of cells folded proteins hence causing spongiform
encephalitis.
*involves making out the surface of the interior G *Bioinformatics genomics (and proteomics);
to make specimen visible in EM to analyze sequence data
B *Yeast two-hybrid systems used to analyze
*Biochem: bc of chemicals and processes protein-protein interactions
needed to make that shape to be viewed in EM

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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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