Endy, MIT BE, 20 May 2004 1 Application Struggle, Limited Success, Struggle… System?? Devices?...
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1Endy, MIT BE, 20 May 2004
Application
Struggle, Limited Success, Struggle…
System??Devices?Design &
Fabrication
2Endy, MIT BE, 20 May 2004
Application
Struggle, Success, Predictable Success
SystemsParts & Fabrication
Design Applications
Tools Registries
Synthesis
Measurement
3Endy, MIT BE, 20 May 2004
• 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
Enabling Biological Engineering
4Endy, MIT BE, 20 May 2004
Abstraction Hierarchy
Devices
Parts
Systems
5Endy, MIT BE, 20 May 2004
Parts
Zif268, Paveltich & Pabo c. 1991
6Endy, MIT BE, 20 May 2004
Devices
cI-857OLac RBS T
CILacI
LacI
CI
7Endy, MIT BE, 20 May 2004
Devices
LacI CI inverter
CILacI
8Endy, MIT BE, 20 May 2004
Systems
Inverter.2 Inverter.3Inverter.1
9Endy, MIT BE, 20 May 2004
Interfaces
Devices
Parts
SystemsInv.2 Inv.3Inv.1
Zif268, Paveltich & Pabo c. 1991
LacI CI
inverterCILacI
10Endy, MIT BE, 20 May 2004
Parts/Device Interface
Devices
Parts
Zif268, Paveltich & Pabo c. 1991
LacI CI
inverterCILacI
X X
A B inverter
BA
11Endy, MIT BE, 20 May 2004
Device/System Interface
Devices
Systems Inv.2 Inv.3Inv.1
A B inverter
BA
C D inverter
DC
E F inverter
FE
12Endy, MIT BE, 20 May 2004
Device/System Interface
Devices
Systems E F C DA B
A B inverter
BA
C D inverter
DC
E F inverter
FE
X X
X
13Endy, MIT BE, 20 May 2004
Device/System Interface
Devices
Systems E F C DA B
A B inverter
BA
C D inverter
DC
E F inverter
FE
A D
X X
X
14Endy, MIT BE, 20 May 2004
Device/System Interface
cI-857OLac RBS T
cILacI
cI-857RBS T
cI
O
PoPSin
PoPSout
LacI
cIPoPSout
PoPSin
15Endy, MIT BE, 20 May 2004
cIRBST
O
PoPSOUT
PoPSIN
cI
PoPSOUT
INVERTER
PoPSOUTPoPSIN
PoPSIN
Polymerase Per Second = PoPS!
16Endy, MIT BE, 20 May 2004
Device/System Interface
Devices
SystemsB CA
A
B
C
PoPSIN
PoPSIN
PoPSIN
PoPSOUT
PoPSOUT
PoPSOUT
X
17Endy, MIT BE, 20 May 2004
Interfaces
Devices
Parts
Systems PoPS Inv.2
PoPS Inv.3
PoPS Inv.1
Zif268, Paveltich & Pabo c. 1991
PoPSInv.1PoPS PoPS
18Endy, MIT BE, 20 May 2004
E.colibrator, Polkadorks @ IAP 2004
QuickTime™ and aVideo decompressor
are needed to see this picture.
19Endy, MIT BE, 20 May 2004
Device-Level System Diagram
20Endy, MIT BE, 20 May 2004
Parts- and Device-Level System Diagram
21Endy, MIT BE, 20 May 2004
DNA Layout
22Endy, MIT BE, 20 May 2004
System-Level Timing Diagram
23Endy, MIT BE, 20 May 2004
Population-Level Simulations
QuickTime™ and aVideo decompressor
are needed to see this picture.
24Endy, MIT BE, 20 May 2004
Trigger Test Circuit
Characterization and Debug
25Endy, MIT BE, 20 May 2004
MIT Registry of Standard Biological Parts
http://parts.mit.edu/
26Endy, MIT BE, 20 May 2004
DNA Synthesis
100
1000
10000
100000
1000000
10000000
1980 1985 1990 1995 2000 2005 2010
Year
Bases of DNAPer Person Day
Carlson, Pace & Proliferation of Biological Technologies, Biosec. & Bioterror. 1(3):1 (2003)
27Endy, MIT BE, 20 May 2004
Hacking the Living World?
28Endy, MIT BE, 20 May 2004
Risk
Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Manipulation
Analysis
Response
Detection
29Endy, MIT BE, 20 May 2004
Biological Risk: Tactics as “Strategy”
Maginot LineFrance, 1940
Ciprofloxacin
Smallpox vaccine
Anthrax vaccine
SARS assay
VHF therapy(under construction)
Plague vaccine(under construction)
30Endy, MIT BE, 20 May 2004
Biological Risk: Future Strategy
Risk
Technology Classes Relevant to Future Biological Risk
(needed capabilities)
Detection
Analysis
Response
Manipulation
31Endy, MIT BE, 20 May 2004
Biological Risk: Suite of Solutions
Nu
mb
er
of
Ind
ivid
uals
Individual’s Intenthonorable dishonorable
Bin Laden Genetics, Inc.
DisgruntledResearcher
Garage Bio-
Hacker
BasicResearch
er
32Endy, MIT BE, 20 May 2004
A Constructive Society
33Endy, MIT BE, 20 May 2004
SacI
D1L BstEII
D1R
A0
D2L SphI
63
TR/SRL
D2R
øOL
D3L BspDI
35
D3R
A1
D4L HindIII
88
D4R
A2
D5L BssHII
316
R0.3BoxA
D6L SexAI
D5R
0.3
370
D7L MluI
D6R
0.4
183
D8L BsiWI
D7R
0.5
158
R0.5
52
D9L RsrII
D8R
0.6A/B
355
D9.5L SacII
D9R
0.7
1102
D10L EagI
D9.5R
91
CR1
D10.5L PacI
D10R
1
2708
D11L EcoRI
D10.5R
139
ø1.1A ø1.1BR1.1
D12L PfoI
D11R
1.1
148
D13L EcoO1091
D12R
1.2
275
D14L XmaI
D13R
80
ø1.3R1.3
D15L ApaI
D14R
1.3
1099
D16L NcoI
D15R
TE
65
D17L KasI
D16R
1.4
173
D19L AatII
D18R
1.5
110
D21L AgeI
D20R
1.6
279
D21R
1.7
164
D17R
ø1.5
D18L AvrII
35
D19R
ø1.6
D20L XbaI
35
A2
210 443
NheI NsiI PciI MfeI ApaLI SpeI SapI BclI
D23L AvrII
D24L EcoRI
D26L BamHI
D27L EagI
D28L SacII
D30L SalI
D22L BstEII D22R D23R D24R D26R D27R D28R D30R
ø2.5 32.8ø3.8
3.5 3.8R3.8
D25L XmaI D25R
2.5
D29L PciI D29R
1.8 2
BglII
175 209 35 723 438 464 478 75 306 75
D32L EagI
D33L AscI
D35L HindIII
D36L PfoI
D37L NheI
D43L XmaI
D31L BsiWI D31R D32R D33R D35R D36R
D40R
4.7 5.7
D34L SgrID34R
4.5
D41L SacII
D42R
4A/4B/4.1/4.2 4.3
1762 35 213 270 69 408 478 903 73
Ø4c Ø4.3 Ø4.7R4.7
D38L SphI
D37R
5
2115
D39L NcoI
D38R
5.3
357
D40L BamHI
D39R
5.5
464
D42L ApaID41R
5.9
464
6
D44L SacI
D43R
114
6.3Ø6.5
R6.5
D45L XhoID44R
D46L EcoRI
D45R
255
6.5
D47L PvuI
D46R
267
6.7
D48L RsrII
D47R
402
7
D49L PstI
D48R
300
7.3
D49R
7.7
223 172
BstEIIXbaI AauI BglI EciI ScaIAvaI SpeI AatI XcaI NsiI
FspI AvrIID50L BsiWI
D51L PvuI
D53L SacII
D54L BamHI
D55L XmaI
D57L HindIIID50R D51R D53R D54R D55R D57R
ø9 10A Tø 12
D52L EcoRI D52R
9
D56L ApaI D56R
8
PacI
1611 35 1038 35 464 73 591 2382 3
ø10 11
DraI RsrIIXbaI
BssHII AatII AvaIBspHI EciINsiI
NdeI
AseI
D57L HindIII
D59L EcoRI
D58L PfoID57R D58R
12 13
PacI
2382 62 4173
ø13R13
D60L BsiWI
D62L EagID59R D60R D62R
16
D61L PvuI D61R
15
ApaLI
591 2244 3520 437
14
NciIScaI
BstBIAvaI
D64L HindIII
D65L BamHI
D67L ApaI
D68L EcoRI
D69L BsiWI
D71L SalI
D63L SacII D63R D64R D65R D67R D68R D69R D71R
ø17 18.5/18.718E
19/19.2/19.3 19.5R18.5
D66L XmaI D66R
17.5
D70L PstI D70R
17
35 1662 204 270 53 460 1761 35 150
øOR SRR/TR
160
KasI BspDIFspIBglI
BlpI DraIII AcvI AciI KpnI
34Endy, MIT BE, 20 May 2004
Kuroda-Kawaguchi et al., Nature Genetics 29:279 (2001)
35Endy, MIT BE, 20 May 2004
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)