1 ndy, MIT April 2005 Drew Endy [email protected] http://mit.edu/endy/www/talks/ file here [.ppt] http://parts.mit.edu/ Registry of Standard Biological Parts April 11, 2005 MIT Policy Opportunities Related to the Engineering of Biology
Jan 13, 2016
1Endy, MIT April 2005
Drew [email protected]
http://mit.edu/endy/www/talks/ file here [.ppt]
http://parts.mit.edu/ Registry of Standard Biological Parts
April 11, 2005MIT
Policy Opportunities Related to the Engineering of Biology
2Endy, MIT April 2005
3Endy, MIT April 2005
4Endy, MIT April 2005
Previous Page
Sequence (BNL)
Dunn & Studier, J. Mol. Bio. 166:477 (1983)
5Endy, MIT April 2005
Wild-Type T7 Genes 2.8-3
----------------2.8----------------->acgcaaagggaggcgacatggcaggttacggcgctaaaggaatccgaaa <--3-RBS---><----------------3--------------
6Endy, MIT April 2005
Wild-Type T7 Genes 2.8-3
----------------2.8----------------->acgcaaagggaggcgacatggcaggttacggcgctaaaggaatccgaaa <--3-RBS---><----------------3--------------
T7.1 Parts 28 & 29
acgcaaGgggagAcgacaCggcaggttacggcgctaaggatccggccgcaaagggaggcgacatggcaggttacggcgctaaa----------------2.8-----------------><D28R|D29L><--3RBS------><---------------3----
7Endy, MIT April 2005
A0TR/SRL
øOL A1 A2 R0.3BoxA 0.30.4 0.5R0.5 0.6A/B 0.7CR1 1
ø1.1A ø1.1BR1.1 1.11.2
ø1.3R1.3 1.3 TE 1.4 1.5 1.61.7ø1.5 ø1.6A2
NsiI PciI MfeI SpeI BclI
B
8Endy, MIT April 2005
A0
63
TR/SRL
øOL
35
A1
88
A2
316
R0.3BoxA 0.3
370
0.4
183
0.5
158
R0.5
52
0.6A/B
355
0.7
1102 91
CR1 1
2708 139
ø1.1A ø1.1BR1.1 1.1
148
1.2
275 80
ø1.3R1.3 1.3
1099
TE
65
1.4
173
1.5
110
1.6
279
1.7
164
ø1.5
35
ø1.6
35
A2
210 443
NsiI PciI MfeI SpeI BclI
9Endy, MIT April 2005
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
10Endy, MIT April 2005
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
11Endy, MIT April 2005
Section alpha Section beta
(1 8,311 bp) (8,311 12,179 bp)
12Endy, MIT April 2005
Wild-Type T7 (T7+) Refactor[1-12,179]:T7+
13Endy, MIT April 2005
Kuroda-Kawaguchi et al., Nature Genetics 29:279 (2001)
14Endy, MIT April 2005
Nature & Change
- Pre-existing- Immutable- Changing- Evolution
Human & Engineer
- Pre-existing- Immutable- Changing- Evolution- Rational design- New- Decoupled
[e.g., disposable]
Nature & Form
- Pre-existing- Immutable
15Endy, MIT April 2005
Carlson, Pace & Proliferation of Biological Technologies, Biosec. & Bioterror. 1(3):1 (2003)
16Endy, MIT April 2005
Goto PartsGoto NCBI. Goto BH Goto Cinnagen
17Endy, MIT April 2005
• 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
18Endy, MIT April 2005
Biological Risk
(1) Past and ongoing work- Breeding- Animal release- Recombinant DNA technology
(2) Liberal democracy in context of living world
19Endy, MIT April 2005
Risk
Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Manipulation
Analysis
Response
Detection
20Endy, MIT April 2005
Risk
Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Analysis
Response
Detection
Manipulation
21Endy, MIT April 2005
Biological Risk: Tactics as “Strategy”
Maginot LineFrance, 1940
Ciprofloxacin
Smallpox vaccine
Anthrax vaccine
SARS assay
VHF therapy(under construction)
Plague vaccine(under construction)
22Endy, MIT April 2005
Risk
Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Analysis
Response
Detection
Manipulation
23Endy, MIT April 2005
Biological Risk: Future Strategy
Risk
Technology Classes Relevant to Future Biological Risk
(needed capabilities)
Detection
Analysis
Response
Manipulation
24Endy, MIT April 2005
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
25Endy, MIT April 2005
Biological Risk: Hack the Living World?
26Endy, MIT April 2005
27Endy, MIT April 2005
28Endy, MIT April 2005
From: XXXXSubject: Endy LetterDate: January 6, 2005 9:45:17 AM ESTTo: [email protected]
Dr. Endy,
I am a sophomore at XXXXX High School in Connecticut and have recently taken an interest in Synthetic Biology.I am writing to ask for your help because i am having difficulty in obtaining information,and understanding some of the information i already have. Anything you can send my way would be greatly appreciated…
…I will soon begin working on a proposal to create a BioBrick, any information you can send me on their creation would be excellent.
-Sincerely, XXXX XXXX XXXX High School -Grade 10
29Endy, MIT April 2005
A Constructive Society
30Endy, MIT April 2005
A Constructive Society
31Endy, MIT April 2005
UT SB Competition Team
c/o Jeff Tabor
32Endy, MIT April 2005
Photons
PoPS
Light PoPSReceiver
PoPS ColorConverter
BBa_I15010BBa_R0082
BBa_B0034BBa_E0033BBa_B0015
UT SB Competition Team
c/o Jeff Tabor
33Endy, MIT April 2005
Lens ripped off of overhead projector
Casserole dishPile of cells/agar
Thermostable chassis
UT SB Competition Team
c/o Jeff Tabor
34Endy, MIT April 2005
UT SB Competition Team
c/o Jeff Tabor
35Endy, MIT April 2005
2003 - MIT IAP (Blinkers)2004 - MIT IAP (Polkadots)2004 - BU, Caltech, MIT, Princeton, UT Austin (FSMs)2005 - Intercollegiate Genetically Engineered Machine (iGEM) Competition
CaltechDavidsonHarvardMITTorontoUCSF/SFSUUT Austin
2006 - Intercollegiate Genetically Engineering Machine (iGEM) Competition
iGEM 2005, 2006, …
OklahomaPrincetonCambridgeETH ZurichPenn StateUC Berkeley
36Endy, MIT April 2005
• Technology Opportunities – General Infrastructure Supporting the Engineering of Biology
• Built from early days with foresight– Detection, Analysis, Response
• Students running a bio-detector on the corner of Ames & Main
• Education Opportunities
– Undergraduate Program in Biological Engineering– Code of Ethics & Standards of Practice for Biological Engineers
• Would likely need to be backstopped by a professional society(s)
• Policy Opportunities– Coherent (?!) organization of federal funding– Integration of research and policy– Broad societal acceptance of responsibility for manipulating genetic
information– International transparency?– Transition from “threat specific” to “capabilities-based” strategy– Distribution of technology? Open or closed?
37Endy, MIT April 2005
Acknowledgements
I would like to acknowledge Adam Arkin, Frances Arnold, Ralph Baric, Roger Brent, Jehoshua Bruck, Carlos Bustamante, Barry Canton, Rob Carlson, Leon Chan, Austin Che, Jim Collins, Lynn Conway, Ron Davis, Mita Desai, John Doyle, Eric Eisenstadt, Michael Elowitz, Stephanie Forrest, Timothy Gardner, Seth Goldstein, Homme Hellinga, George Homsy, Joe Jacobsen, Tom Kalil, Jay Keasling, Heather Keller, 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, other members of the lab and the MIT Synthetic Biology Working Group, and the students and instructors of the 2003/4 MIT IAP Synthetic Biology Labs and the 2004 Synthetic Biology Competition for their direct contributions to the material presented here and to my current thinking about how to best engineer biology.