Benefits to Cadence of the MIT MAP-Chip Project

1
Design of Self-Replicating Machines
SRM
time
2
Consider a Cell
Signaling Pathway
Yeast
Cell Cycle
3
Consider a Different Cell
Yeast
Yet Another Signaling Pathway
Budding
Cell Cycle
Metabolism
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What does T7 know?
SRMT7
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F. William Studier, Science 176403 (1972)
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Previous Page
Sequence (BNL)
Dunn Studier, J. Mol. Bio. 166477 (1983)
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What do we know?
SRMT7
What We Need To Know
What We Know
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Genome Domestication
What We Make SRMT7-SB
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NsiI
MfeI
SpeI
øOL
A1
A2
C
ø1.1A
ø1.1B
ø1.3
ø1.5
ø1.6
A2
B
TR/ SRL
R0.3
BoxA
0.3
0.4
0.5
R0.5
0.6A/B
0.7
R1
1
R1.1
1.1
1.2
R1.3
1.3
TE
1.4
1.5
1.6
1.7
A0
11
NsiI
MfeI
SpeI
63
35
35
88
316
370
183
158
52
355
1102
91
2708
139
148
275
80
1099
65
173
110
279
164
35
210
443
øOL
A1
A2
C
ø1.1A
ø1.1B
ø1.3
ø1.5
ø1.6
A2
A0
TR/ SRL
R0.3
BoxA
0.3
0.4
0.5
R0.5
0.6A/B
0.7
R1
1
R1.1
1.1
1.2
R1.3
1.3
TE
1.4
1.5
1.6
1.7
12
NsiI
MfeI
SpeI
SacI
NheI
ApaLI
SapI
63
35
35
88
316
370
183
158
52
355
1102
91
2708
139
148
275
80
1099
65
173
110
279
164
35
210
443
øOL
A1
A2
C
ø1.1A
ø1.1B
ø1.3
ø1.5
ø1.6
A2
A0
TR/ SRL
R0.3
BoxA
0.3
0.4
0.5
R0.5
0.6A/B
0.7
R1
1
R1.1
1.1
1.2
R1.3
1.3
TE
1.4
1.5
1.6
1.7
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Rebuild1-8311T7
T7
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D64L HindIII
D65L BamHI
D67L ApaI
D68L EcoRI
D69L BsiWI
D71L SalI
D63L SacII
D66L XmaI
D70L PstI
D63R
D64R
D65R
D67R
D68R
D69R
D71R
D66R
D70R
BglI
35
1662
204
270
53
460
1761
35
150
160
E
ø17
øOR
18.5/18.7
18
19/19.2/19.3
19.5
R18.5
17.5
17
SRR/TR
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E.colibrator, Polkadorks _at_ IAP 2004
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Struggle, Limited Success, Struggle
Devices?
System??
Design Fabrication
Application
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Struggle, Success, Predictable Success
Applications
Systems
Parts Fabrication
Design
Application
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Enabling Biological Engineering

• Standardization of Components
• Predictable performance
• Off-the-shelf
• ME, 1800s
• Abstraction
• Insulate relevant characteristics from
  overwhelming detail
• Simple artifacts that can be used in combination
• From Physics to EE, 1900s
• Decoupling Design Fabrication
• Rules insulating design process from details of
  fabrication
• Enable parts, device, and system designers to
  work together
• VLSI electronics, 1970s

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Abstraction Hierarchy
Systems
Devices
Parts
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Parts
Zif268, Paveltich Pabo c. 1991
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Devices
CI
LacI
l cI-857
OLac
RBS
T
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Devices
LacI ? CI inverter
LacI
CI
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Systems
Inverter.2
Inverter.3
Inverter.1
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Interfaces
Systems
Inv.2
Inv.3
Inv.1
LacI ? CI inverter
LacI
CI
Devices
Parts
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Parts/Device Interface
LacI ? CI inverter
LacI
CI
Devices
Parts
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Stories
In 1910, I was in Mexico, in the state of
Yucatan, when an invasion of locusts occured
the Indians reported to me that in a certain
place the ground was strewn with the corpses of
these insects. I went there and collected sick
locusts, easily picked out since their principal
symptom was an abundant blackish diarrhoea. This
malady had not as yet been described, so I
studied it. It was a septicaemia with intestinal
symptoms, It was caused by bacteria, the locust
coccobacilli, which were present almost in the
pure state in the diarrhoeal liquid. I could
start epidemics in columns of healthy insects by
dusting cultures of the coccobacillus on plants
in front of the advancing columns the insects
infected themselves as they devoured the soiled
plants In the course of these researches, at
various times I noticed an anomaly, shown by some
cultures of the coccocacillus which intrigued me
greatly, although in fact the observation was
ordinary enough., so banal indeed that many
bacteriologists had certainly made it before on
a variety of cultures. The anomaly consisted of
clear spots, quite circular, two or three
millimeters in diameter, speckling the cultures
grown on agar. -- The Bacteriophage by Dr. Felix
d'Herelle, Science News 14 44-59 (1949).
(Translation by J. L. Crammer)
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Parts/Device Interface
LacI ? CI inverter
LacI
CI
Devices
X
X
Parts
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Device/System Interface
Inv.2
Inv.3
Inv.1
Systems
Devices
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Device/System Interface
X
E ? F
C ? D
A ? B
X
X
Systems
Devices
34
Device/System Interface
A ? D
E ? F
C ? D
A ? B
X
X
Systems
X
Devices
35
Device/System Interface
36
Polymerase Per Second PoPS!
PoPSOUT
PoPSIN
T
l cI
RBS
Ol
cI
PoPSOUT
PoPSIN
INVERTER
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PoPS Fan-In
38
PoPS Fan-Out
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PoPS-based Composition
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Device/System Interface
Systems
X
Devices
41
Device/System Interface
Systems
X
A
PoPSOUT
Devices
PoPSIN
B
PoPSOUT
PoPSIN
C
PoPSIN
PoPSOUT
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Interfaces
Systems
PoPS Inv.2
PoPS Inv.3
PoPS Inv.1
PoPS Inv.1
Devices
PoPS
PoPS
Parts
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E.colibrator, Polkadorks _at_ IAP 2004
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Device-Level System Diagram
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Parts- and Device-Level System Diagram
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DNA Layout
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Population-Level Simulations
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Characterization and Debug
Trigger Test Circuit
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MIT Registry of Standard Biological Parts
http//parts.mit.edu/
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DNA Synthesis
Bases of DNA Per Person Day
Year
Carlson, Pace Proliferation of Biological
Technologies, Biosec. Bioterror. 1(3)1 (2003)
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Hacking the Living World?
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Biological Risk Background
Technology Classes Relevant to Biological
Risk (current relative capabilities)
Risk
Manipulation
Detection
Analysis
Response
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Biological Risk Tactics as Strategy
Maginot Line France, 1940
Anthrax vaccine
SARS assay
Ciprofloxacin
VHF therapy (under construction)
Smallpox vaccine
Plague vaccine (under construction)
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Biological Risk Future Strategy
Technology Classes Relevant to Future Biological
Risk (needed capabilities)
Risk
Manipulation
Detection
Analysis
Response
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Biological Risk Suite of Solutions
Basic Researcher
Garage Bio-Hacker
Disgruntled Researcher
Number of Individuals
Bin Laden Genetics, Inc.
Individuals Intent
honorable
dishonorable
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A Constructive Society
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D64L HindIII
D65L BamHI
D67L ApaI
D68L EcoRI
D69L BsiWI
D71L SalI
D63L SacII
D66L XmaI
D70L PstI
D63R
D64R
D65R
D67R
D68R
D69R
D71R
D66R
D70R
BglI
35
1662
204
270
53
460
1761
35
150
160
E
ø17
øOR
18.5/18.7
18
19/19.2/19.3
19.5
R18.5
17.5
17
SRR/TR
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Kuroda-Kawaguchi et al., Nature Genetics 29279
(2001)
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Responsibility
Men have forgotten this truth, said the fox.
But you must not forget it. You become
responsible, forever, for what you have tamed.
Saint-Exupéry, Le Petit Prince (1943)
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Acknowledgements
Lab Jennifer Braff, Barry Canton, Leon Chan,
Caitlin Conboy, Jeffrey Gritton, Alison Hearn,
Heather Keller, Jason Kelly, Sriram Kosuri, Maia
Mahoney, Sara Neves, Sylvain Olier, Jose Pacheco,
Francois St-Pierre, Samantha Sutton, Ilya
Sytchev, and Ty Thomson Others Adam Arkin,
Frances Arnold, Ralph Baric, Roger Brent,
Jehoshua Bruck, Carlos Bustamante, Rob Carlson,
Austin Che, Jim Collins, Lynn Conway, Ron Davis,
Mita Desai, Eric Eisenstadt, Michael Elowitz,
Felice Frankel, Stephanie Forrest, Timothy
Gardner, Seth Goldstein, Homme Hellinga, George
Homsy, Joe Jacobsen, Tom Kalil, Jay Keasling,
Doug Kirkpatrick, Tom Knight, Sri Kosuri, Patrick
Lincoln, John Mulligan, Richard Murray, Radhika
Nagpal, Richard Newton, Carl Pabo, Randy
Rettberg, Pamela Silver, Brad Smith, Christina
Smolke, Gerry Sussman, Samantha Sutton, Claire
Tomlin, Jeffrey Way, Chris Webb, Ron Weiss, Scot
Wolfe, Aarne Vesilind, the members of the MIT
Synthetic Biology Working Group, and the students
of the 2003 and 2004 MIT IAP Synthetic Biology
Labs