Model Organisms & Tools of
Cell Biology
Lecture 3
Autumn 2007
Learning the Unknown
You are a car mechanic
 Would you rather know a little bit about
the working of every car every
constructed…
 … or everything about a representative
one from each category?
 Science is no different!
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What is a Model Organism?
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Many aspects of biology are similar in most or
all organisms
It is much easier to study particular aspects in
particular organisms - for instance, genetics is
easier in small organisms that breed quickly,
and very difficult in humans!
The most popular model organisms have strong
advantages for experimental research
They become even more useful when other
scientists have already worked on them,
discovering techniques, genes and other useful
information.
How many are there?
Many (about 80)
 Mouse, rat, zebra fish, viruses, chicken,
dog, hamster, slime mould, maize,
tetrahymena, etc.
 Many scientists have worked on all these
over the years, and shared information
extensively
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Which are the main ones?
1) E. coli (bacterium)
 2) Saccharomyces cerevisiae (yeast)
 3) Arabidopsis thaliana (weed)
 4) Drosophila melanogaster (fruit fly)
 5) Mus musculus (mouse)
 6) Homo sapiens (Man)
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Arabidopsis thaliana
(mustard plant)
01_33_model plant.jpg
This is now the main
model plant system for
genetics.
Its small genome, and
the recent application of
classical genetics has
put it far ahead of other
models of agricultural
importance (tomato,
tobacco, corn etc.)
It's genome has been
fully sequenced.
Drosophila sp.
‘Fruit Fly’
Usually the species
Drosophila
melanogaster Easily raised in lab,
rapid generations,
mutations easily
induced, many
observable mutations.
Many clues to
development and
genetics
01_34_Drosophila.jpg
01_38_C.elegans.jpg
Caenorhabditis elegans, a nematode
(Usually called just C. elegans)
-an excellent model for understanding the
genetic control of development and physiology.
-C. elegans was the first multicellular organism
whose genome was completely sequenced
-First to show fixed cell count in body
-Gave important clues on programmed cell
death
Saccharomyces cerevisiae, baker's yeast or
budding yeast (used in brewing and baking)
01_32_model eucaryote.jpg
Early studies on this enabled us to get a great grasp on the cell cycle
Humans
• Regardless of how thoroughly we may
understand other animal systems, sometimes
there is no alternative but to study humans
directly - i.e. breast cancers
• The human animal is the most medically
analyzed and documented of any species.
• We have now completely sequenced our
own genome too
• Over the next decade or so we will
understand more about our biology than ever
before!
Where has knowledge of cells
come from?
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Can we see cells?
Yes and no, most are too small, but some we
can see easily - the egg of a chicken is a large
single cell
What are ‘The tools of Cell Biology’?
How big is the average egg?
Lets put it in perspective…
Size perspective
1X
1000X organelles
100X - cells
100,000X proteins
1,000,000X atoms
10X -tissues
10,000X organelles
Microscopes - aid us in seeing
First cells seen by Robert Hook, who
made the first compound microscope
 He looked at cork cells
 The detail was lacking and limited by the
quality of the instrument
 Light microscopes are now much better
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Light Microscopes
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QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Many types exist
Light is either reflected from the specimen (Oblique
illumination) or transmitted through the specimen
(Bright field optical microscopy)
How small can we see? We can see all cells.
The lens are so good now that the limiting factor is
now the wavelength of light itself.
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The wavelength of the visible light used in optical
microscopes is between 400 and 700 nanometers (nm).
The resolving powers of high-quality light microscopes
are limited by the wavelength of imaging light to about
200 nanometers
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Electron Microscopes
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Sample placed in vacuum - thus dead
Four main types all using electron streams
instead of light waves;
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Transmission Electron Microscope (TEM)
Scanning Electron Microscope (SEM)
Reflection Electron Microscope (REM)
Scanning Transmission Electron Microscope (STEM)
Resolutions as low as 70pm have been
obtained - single atoms
• Read all about these on the course web site
Centrifugation - for analysis
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Allows separation of
Cells
 Organelles
 DNA and other macromolecules
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Uses gravitational and centrifugal forces
to separate items based on density and
size - one spins things at high speeds
 Many types are used in cell biology…
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Differential centrifugation
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This is the most
common method of
fractionating cells
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Fractionation is
the separation of
the different
organelles within
the cell
The speed
determines which
size and mass
(density) of
material is pelleted.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Isopycnic centrifugation
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Isopycnic centrifugation or equilibrium
centrifugation is a process used to isolate
nucleic acids such as DNA.
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Much high speeds and duration
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Separates DNA based on base
composition
Sucrose gradient centrifugation
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Uses a decreasing
concentration of sucrose
in a tube
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The particles travel
through the gradient until
they reach the point in
the gradient at which
their density matches
that of the surrounding
sucrose.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Other commonly used tools…
Mutation analysis - an important
mechanism for discovery
Any organism which is different from the
norm can be a candidate for biochemical
analysis
 Mutations are generally the cause of such
differences
 By analysis of these mutations one can
gain insights or deduce the biochemical
basis of important pathways…
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Conditional Mutation Analysis - e.g. Temperature conditional
The organism grows at one temperature (permissive) but fails to do so
at a different one (restrictive).
01_35_Yeast mutation.jpg
All the yeast colonies grow at one temperature (23C), but if one places
the same cells at 35C some of the colonies fail to grow - what is
wrong with the ones that fail to grow?
Gain-of-function mutations - e.g. biochemical function
01_36_S. pombe rescued.jpg
Sequence analysis has taught us that there are about 200-300 genes
required for the most basic cell survival.
Comparisons across species shows that many genes are common from
simple bacteria to complex life forms, and that life uses similar processes
01_37_amino acid sequ.jpg
Genome sizes - a genome is the total haploid amount of DNA
Amoeba proteus
290,000,000,000
(100 times the size of a human genome)
Bufo bufo
6,900,000,000
(cane toad)
Homo sapiens
3,000,000,000
(Man)
(3 billion base pairs - 24 chromosomes - [22, X, Y])
Muntiacus muntjak vaginalis (Indian deer)
2,521,500,000
Boa constrictor
2,100,000,000
Quick Time™a nd a
TIFF ( Unco mpre ssed ) dec ompr esso r
ar e nee ded to see this pictur e.
(snake)
Rhinolophus ferrumequinum
1,929,400,000
(bat)
Plasmodium falciparum
25,000,000
(malaria parasite)
Human immunodeficiency virus type 1 (HIV)
19,750
There is no real correlation between the genome size and complexity
01_40_genome sizes.jpg
Genome size and number of genes
Among the organisms whose genomes are sequenced, genome size does not
correlate with the number of genes.
Species
Human
Size of genome
3.0 billion base pairs
Fruit fly (Drosophila melanogaster)
120 million base pairs
Baker's yeast (Saccharomyces cerevisiae)
12 million base pairs
Worm (Caenorhabditis elegans)
97 million base pairs
E. coli
4.6 million base pairs
Arabidopsis (Arabidopsis thaliana)
125 million base pairs
Number of genes
25,000 ?
13,601
6, 275
19,000
4,403
25,000
Study…
Please read chapter 1 entirely, if you have
not done so already
 Sample questions for the exams will start
appearing on the supporting web site this
week!
 Bye!
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