Download MolBioIntro

Introduction to Synthetic Biology
x23 Series
Herbert Sauro
http://sys-bio.org/bioencseee-423523486586in-2013/
Syllabus
Week 1/2: Essential Molecular Biology and Introduction
a) What is life?
b) Evolutionary time scale
c) DNA, RNA and proteins
d) The cellular context
e) Engineering DNA
f) What is Synthetic Biology?
g) Applications and ethical issues
Week 3: Modeling Synthetic Circuits
a) The need for modeling in synthetic biology
b) Stochastic and deterministic models
c) Models of gene regulatory networks
d) Software and modeling techniques
e) Example simulations
Syllabus
Week 4/5: Synthetic Biology Circuits
a) Basic circuit, repression and activation
b) Feed-forward circuits
c) Switches
d) Oscillators
e) Logic gates
Week 6/7: Assembling a System: case study to build a working system
a) Design objective
b) The components
c) The simulation
d) DNA assembly methods
e) Testing
Syllabus
Week 8: Components and Standardization
a) Standards in Engineering
b) The need for standards in synthetic biology
c) Examples of existing standards, biobricks, SBOL, Registry, GenBank, etc
d) Variety of components used in synthetic biology
Week 9: Practical Issues in Creating Devices
a) Computer aided design and workflows
b) Orthogonality, Robustness, Tunability, Compatibility, Fan-Out, Signal Impedance
c) Noise in biological systems
Week 10:
What is Life?
Traditional View (Wikipedia):
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The ability to move; plants turn toward light, sponges' collar cells' flagella turn
round, fungi (exc. the little pot fungi, which have flagellate spores)
and bacteria without locomotory apparatuses... huh.
The ability to respire, turning nutrients into energy. For life on Earth, this process
is glycolysis, and the storage of energy is maintained by ATP.
Sensitivity to the outside world, and an ability to react. Lions maul you if you poke
them with a stick, plants will grow their roots out, E. coli bacteria will change
direction toward sugar and away from acid.
Growth is self-explanatory; seeds or spores turn into plants or fungi or whatever,
cute babies turn into annoying teenagers, bacteria... huh.
Reproduction is also self-explanatory; amoebae undergo mitosis, plants release
pollen to fertilise other plants, bacteria divide, mules and sterile humans... huh.
Respiration generates waste, which is excreted or otherwise removed from the
organism. Diffusion is a legitimate way to do this.
To meet the above characteristics, the organism needs nutrition. Even plants are
going to need water and minerals.
What is Life?
Modern View:
• “self-sustaining chemical system capable of
Darwinian evolution.” : Carl Sagan, Bruce
Jokosky
• “self-sustaining system capable of Darwinian
evolution.”
Minimal Life Form
Timeline
4.54
3.8
3.5
2.4
1.8
0.6
Billions of Years
Humans
First Life
Multicellular Organisms
Oxygen in
Atmosphere
Blue-green
Algae
Formation of Earth
Eukaryotic Cells
Timeline
}
Typical Bacterium
Typical Animal Cell
Typical Plant Cell
Eulena: Protist
Amoeba: Protist
Paramecium: Protist
Characteristics of Earth Life
• Liquid/Gel state
• Chemistry
• Massively Parallel
Molecules
Small molecules
Source of energy or material, structural components, signal transmission,
building blocks of macromolecules
Water, sugars, fatty acids, amino acids, nucleotides
Proteins
Main building blocks and functional molecules of the cell
Structure, catalysis of chemical reactions, signal transduction,
communication with extracellular environment
Molcules
• DNA
– Storage and reproduction of information
• RNA
– Intermediary molecule between DNA and protein
Central Dogma
Sequence of nucleotides
Backbone is composed of sugars, linked to each other via phosphate bonds
Each sugar is linked to a base
Adenine (A), Thymine(T), Guanine (G), Cytosine (C)
The Double Helix
DNA is generally found in a double strand form
A and T, C and G form hydrogen bonds
Two strands with complementary sequences run in opposite
directions
5’ A-T-C-T-G-A 3’
3’ T-A-G-A-C-T 5’
They are coiled around one another
to form double helix structure
Genomes
Organism
Viruses
Prokaryotes
Eukaryotes
MS2
Lambda
Smallpox
M. genitalium
E. coli
S. Cerevisiae (yeast)
Arabidopsis
Human
Maize
Lily
Genome Size (KB)
No. of Genes
4
50
267
580
4,700
12,068
100,000
3,000,000
4,500,000
30,000,000
~30
~ 200
470
4,000
5,885
20 -30,000
~ 100,000
~ 30,000
RNA
– RNA is made of ribonucleic acids instead of
deoxyribonucleic acids (as in DNA)
• RNA is single-stranded
• In RNA sequences, Thymine (T) is replaced by Uracil (U)
– mRNA carries the message from genome to
proteins
– tRNA acts in translation of biological
macromolecules from the language of nucleic
acids to amino acids
Proteins
– Proteins are chains of amino acids connected by
peptide bonds
• Often called a polypeptide sequence
• There are 20 different types of amino acid molecules (each
amino acid in the chain is commonly referred to as a residue)
– Proteins carry out most of the tasks essential for life
• Structural proteins: Basic building blocks
• Enzymes: Catalyze chemical reactions that enable the
mechanism transform forms of matter and energy to one
another (metabolism)
• Transcription factors: Genetic regulation, i.e., control of
which protein will be synthesized to what extent
Amino Acids
20 Amino Acids
Protein Structure
Protein Stucture
Size Variation
http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/poster_quickref.pdf