Transcript ch1 FA11 - Cal State LA

Intro to Cell & Molecular Biology
• How do we study cell biology?
– Reductionist view
• Cells as tiny complex machines
• Sum of parts = whole
• Your goal:
– be able to explain the roles
various molecular parts play in
cell biological processes
– With the same comfort and
familiarity as with
macroscopic items (trains,
stoves, bicycles, etc…)
Intro to Cell & Molecular Biology
• How do we study cell biology?
– Parsimony
• the simplest explanation for all
relevant data is preferred over
more complex explanations
• The most parsimonious answer
is not necessarily perfectly
correct
• More data could make us
revise it
Intro to Cell & Molecular Biology
• An example of parsimony in action
– How did I get to class today?
• Data: Someone saw me in the parking garage
• Data: You can see that I’m here now
• More parsimonious answer
– Drove to campus, walked straight to class
• Less parsimonious answer
– Drove to campus, went to Starbucks, checked email in office,
wandered around Salazar Hall lost for awhile, finally found
classroom
Intro to Cell & Molecular Biology
• However, if someone else can add more observations:
• Data: I have a cup from Starbucks
• Data: I was seen in my office before class
• More parsimonious answer
– Drove to campus, went to Starbucks, checked email in office,
found classroom
• Still less parsimonious to include
– wandered around Salazar Hall lost for awhile
…unless someone has additional data to add…
The Discovery of Cells
• Cell theory was articulated in the mid1800s by Schleiden, Schwann and Virchow.
– All organisms are composed or one or more
cell.
– The cell is the structural unit of life.
– Cells arise from pre-existing cells by division.
The Discovery of Cells
• An early timeline of important tools
– Microscopes, ~1650s
• Robert Hooke &
• Anton van Leeuwenhoek,
– Human cell culture, 1951
• Henrietta Lacks = HeLa cells
– In vitro (within the glass) experiments are conducted
outside the living organism or with isolated parts of
the organism
– In vivo (within the living) experiments are conducted
on the whole living organism
Intro to Cell & Molecular Biology
• Basic properties of cells
– Complex and organized
– Able to capture and use energy
– Chemical factories
– Genetically programmed
– Responsive to stimuli
– Capable of mechanical work
– Reproductive
– Capable of self-regulation
Intro to Cell & Molecular Biology
• Two structural classes of cells
– Prokaryotic
• “Before” nucleus
Intro to Cell & Molecular Biology
• Two structural classes of cells
– Eukaryotic
• “True” nucleus
A generic animal cell
• Our primary focus of study, comparative approach with bacteria
• A very sophisticated micro-machine
Types of prokaryotes
• Archaea
– Extremophiles (methanogens, halophiles, thermophiles)
• Bacteria (what “prokaryote” makes most people think about)
– Cyanobacteria
– Mycoplasma
Fix CO2 --> CH2O, Fix N2 --> NH3
Smallest living organisms
– Total carbon in bacteria ~ total carbon in plants
cyanobacterium
Types of Eukaryotes
• Single-celled
– Performs all functions
for viability
• Multicellular
– Individual cells
specialize via
differentiation
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•
•
•
Neurons
Hepatocytes
Myotubes
Sperm, Egg
So, who are the prokaryotes?
• Both the Bacteria and the Archaea are prokaryotes
• And they are quite different from each other
Intro to Cell & Molecular Biology
• Two structural classes of cells
– Prokaryotic
• “Before” nucleus
– Eukaryotic
• “True” nucleus
– No known intermediates,
– Common evolutionary ancestry
Model for common evolutionary ancestry
• Anaerobic heterotrophic
prokaryote phagocytoses
an aerobic heterotrophic
prokaryote
• The aerobic heterotroph
escapes into the cytosol of
the “host”
• A symbiotic relationship
gives rise to an aerobic
heterotrophic prokaryote
Model for common evolutionary ancestry
• Plasma membrane
invaginations cluster
genomic DNA into a cellcentral location
• Pinching membrane off
yields a double membrane
structure surrounding the
genomic DNA
Model for common evolutionary ancestry
• Further elaboration of the
double membrane
enclosure yields the
modern nucleus and
endoplasmic reticulum
• Symbiotic capture of a
photosynthetic bacteria and
elaboration of a cell wall
yields plant cells
Evidence for common evolutionary ancestry
• Evidence to support endosymbiont theory
– Absence of eukaryote species with organelles in an intermediate
stage of evolution.
– Many symbiotic relations are known among different organisms.
– Organelles of eukaryotic cells contain their own DNA.
– Organelles duplicate independently of nucleus.
– Nucleotide sequences of rRNAs from eukaryotic organelles
resembles that of prokaryotes.
Parsimony
Stem cells for use in cell replacement therapy
• Two fundamental
stem cell types
– Adult
• Hematopoietic,
muscle, etc
• Very limited
potential
– Embryonic
• Pluripotent stem
cells
• Very broad
potential
Muscle stem cell
Stem cells for use in cell replacement therapy
1. Isolate nucleus from a
normal somatic cell
2. Inject it into an
enucleated oocyte
3. Grow in vitro to
blastocyst stage
4. Isolate ES cells and
grow more in vitro
5. Induce differentiation
in vitro to yield
desired cell type
6. Transplant new cells
back into patient
Stem cells for use in cell replacement therapy
• Induced pluripotent (iPS) cells has been
demonstrated in culture.
– Involves reprogramming a fully differentiated
cell into a pluripotent stem cell.
– These cells have been used to correct certain
disease conditions in experimental animals.
– Studies to reveal the mechanism of iPS could
have significant medical applications.
Steps taken to generate iPS for use in correcting the
inherited disease sickle cell anemia in mice
1.
2.
3.
4.
5.
6.
Collect skin cells
Reprogram into iPS
cells (+ 4 txn factors)
Correct mutation by
genetic engineering
Recover corrected iPS
cells
Differentiate into
hematopoietic stem
cells
Transplant corrected
cells back into host
Cell Size
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•
•
•
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Eukaryote
Nucleus
Mitochondria
Ribosome
DNA
10-30 um diameter
5-10 um diameter
2 um long
30 nm diameter
2 nm wide
• Why are cells so small?
– Limited by diffusion rates
• O2 diffuses 1um in 100 microseconds
• It takes 106 longer to travel 1 mm
• As Volume increases,
• Surface area becomes limiting
Cell Size
• Limited by diffusion rates
– S/V = 3/r
surface/volume
– As Volume increases
• V= 4/3 π r3
– Surface area becomes limiting
• S = 4 π r2
4
3
2
1
0
0
10
20
radius, r
30
Cells find ways to get around the
Surface/Volume problem
Line A:
Line B:
• Which line is longer?
– Cells apply the same idea to plasma membrane topology
An epithelial cell surface
Line A:
Line B: