2007 synthetic biology team challenge march 19-23, 26 instructors: howard salis, jeff tabor
TRANSCRIPT
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2007 Synthetic Biology Team Challenge
March 19-23, 26Instructors: Howard Salis, Jeff Tabor
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Course Information
• Monday – Friday: 9AM-5PM
• Final Presentations: Monday 3/26 1:30-3PM GH 114
• Course wiki: http://openwetware.org/wiki/Jeff_Tabor/UCSF_Synthetic_Biology_Team_Challenge
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Schedule
• Monday– Intro to Synthetic Biology– Lab: Registry of Standard Biological Parts
• Tuesday– Survey of useful parts– Journal Club– Lab: Engineer novel genetic logic
• Wednesday– Modeling gene networks in MATLAB (H. Salis)– Homework: Brainstorm synthetic system
• Thursday– Develop plan for system– Optimize system with model
• Friday– Specify system with appropriate parts from literature– Document parts and systems in the registry– Simulations of final systems
• Monday (1:30-3:00)– ~15 min Final presentations.– 5 Faculty judges decide winner– Winning group’s design is synthesized.
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Outline - Monday
1. Brief History of Molecular Biology
2. Dawn of Synthetic Biology1. Concepts driving early designs2. Building genomes from scratch
3. Landmark efforts in system design
4. System talks1. Liz Clarke2. Dan Widmaier3. Matt Eames
5. Abstracting/formalizing the design process
6. Lunch
7. Afternoon Lab. MIT’s registry of Standard Biological Parts.
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Chronology of Molecular Biology
• 1953. Structure of DNA. Watson and Crick
• 1961. Concept of mRNA, Regulator/operator pairs, Operons. Jacob and Monod.
-(Gene networks of any desired property can be assembled from combinations of simple regulatory elements)
• 1961+. Discovery of codons and the genetic code
• 1973. Recombinant DNA technology (Cohen and Boyer, UCSF)
• 1977. DNA Sequencing Technology.
• 1983. Invention of PCR. "Beginning with a single molecule of the genetic material DNA, the PCR can generate 100 billion similar molecules in an afternoon.“ –K. Mullis
• 1987. First Automated Sequencer (Applied Biosystems Prism 373)
• 1997. Sequence of E.coli genome published (Blattner, UW)
• 2001. Sequence of human genome published (HGP/Celera)
• 2002. CSI:Miami debuts on CBS
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Synthetic Biology
Nature 403, January 2000
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Cells are composed of complex networks
Adapted From: Lee et al., Science, 2004
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Complex networks are composed of simpler modules
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Modules can be reconfigured into synthetic networks
Elowitz and Leibler. Nature, 2000
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Simulating a synthetic gene network
Continuous Model Discreet Model
Elowitz and Leibler. Nature, 2000
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Genetic Toggle Switch
Gardner et al. Nature, 2000
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Carlson, Pace & Proliferation of Biological Technologies, Biosec. & Bioterror. 1(3):1 (2003)
c/o Drew Endy
-DNA synthesis capacity has doubled each 1.5 years over the past 10 years
-System design and fabrication can routinely be decoupled
(Endy, Nature 2005)
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Building genomes from scratch
• 2002. Assembly of functional poliovirus genome (~7.5kb; Cello et al., Science 2002).– Oligos designed computationally, ordered commercially
– [C332652 H492388 N98245 O131196 P7501 S2340]
• 2003. Assembly of a bacteriophage genome (~5kb; Smith et al., PNAS 2003).– 2 weeks assembly time
• 2005. Assembly of the 1918 flu virus (~13kb). (Tumpey et al., Science 2005).
• Craig Venter’s Mycoplasma genitalium genome = 580kb
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Rewriting genomes (Chan et al., Molecular Systems Biology, 2005)
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wt
refactored
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Genetic pulse generator
http://www.pnas.org/content/vol0/issue2004/images/data/0307571101/DC1/07571Movie1.mov
Basu et al., PNAS 2005
Sender E.coli Receiver E.coli
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Genetic pattern formation circuit
Basu et al., Nature 2005
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2004 UT-Austin/UCSF Bugwarz Team
Not pictured: Andy Ellington, Chris Voigt
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High-resolution spatial control of gene expression
Projector
Agar plate Agar plate
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Engineering light-dependent gene expression in E. coli
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Bacterial photography
Wild-typeEnvZ
Mask Bacterial lawn
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“Light Cannon”
Mercury vapor lamp
Concave grating spectrometer
Actuator
Projected image
37 degree incubator
Double Guass focusing lens
35 mm slide
632nm bandpass filter
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Improved black and white photography
Endyrichia coliEscherichia ellington
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‘Biofilm’ capable of continuous expression response
Levskaya et al., Nature, 2005
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Continuous response allows capture of high information images
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Bacterial edge detector
Projector
Agar plate
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Genetic logic for edge detection
Only occursat edge of light/dark
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Gates mismatched: LOW output from gate 1 interpreted as HIGH input at gate 2
Light repression isincomplete
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Matching gates through RBS redesign
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Contributed Talks
• 10:00-10:30: L. Clarke ‘A Bacterial Thermometer’• 10:30-11:00: D. Widmaier ‘Secreting Spider Silk in
Salmonella’• 11:00-11:30: M. Eames ‘Remote Controlled Bacteria’
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Genetic “Parts” for programming living cells
Voigt, Curr. Opin Biotechnol., 2006
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Genetic “devices” integrate signal inputs
Voigt, Curr. Opin Biotechnol., 2006
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Device outputs control “actuators” which determine cellular behaviors
Voigt, Curr. Opin Biotechnol., 2006
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Making Biology a reliable engineering discipline
• Standardization– Composability
• Characterization – ‘off the shelf’ functionality
• Centralization– Well documented repositories
• Abstraction– Distribution of expertise/labor
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Device characterization
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http://parts.mit.edu/registry/index.php/Part:BBa_F2620
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Abstraction hierarchy for the engineering of biology
Endy, Nature 2005
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Lunch
• GH 114
sai