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iGEM,The Registry of Standard Biological

Parts,And Synthetic Biology

Randy RettbergRandy Rettberghq@igem.org

igem.orgigem.org

Cambridge, UKJuly 5, 2010

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Synthetic Biology Question

Can simple biological systems be built from standard, interchangeable parts and operated in living cells?

Or, is biology so complex that each case is unique?

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Education Driving Research

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Device-Level System Diagram 2003

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Parts- and Device-Level System Diagram

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iGEM Philosophy

iGEM Philosophy: Get and Give

Teams are expected to use the parts, ideas, and experience of teams in previous years.

Teams are expected to contribute their parts, ideas, and experiences.

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iGEM 2004 (SBC 04)

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iGEM 2005

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iGEM 2005

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iGEM 2006

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iGEM 2007

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iGEM 2008

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iGEM 2009

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iGEM 2010 Teams - 2

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iGEM AND High School Teams

Advisor: Wendell Lim Advisor: Orion Weiner Advisor: James Onuffer

Teacher at Lincoln High School: George Cachianes Teacher at Lincoln High School: Julie ReisPlus 10 “Buddies”

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Is iGEM Safe?

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Is iGEM Secure?

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IAP

2004

2005

2006

2007

2008

2009

2010

2011

2012

4

5

13

32

54

84

112

130

180

250

20

70

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360

570

825

1100

1300

1800

2500

20

70

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400

750

1180

1650

1950

2700

3700

Year Teams Jamboree Total

iGEM Growth and Scale

iGEM Scale and Growth

Or Not !

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iGEM 2010 and Beyond

− 2010 130 Teams, Jamboree at MIT November 6-8

− 2011 180 (?) Teams,– Regional Jamborees in October– World Championship at MIT (Nov. 5-7)– Regional iGEM Headquarters

− iGEM Labs and Courses– Sign up at ung.igem.org

− iGEM Society, Institution, Foundation− iGEM Alumni Association

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New Synthetic Biologists

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Registry Labs

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Synthetic Biology Courses

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iGEM Community Now

• 7,041 user accounts• 6,513 unique emails• 1,782 users have logged in since Feb 2010• 920 have entered parts

• 12,327 parts entered• 5,166 DNA samples at the Registry• 2,328 reported to work• 1,691 parts sent by last year’s teams• 795 sequence confirmed parts

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The Registry: Quality Not Quantity

Parts in the Registry are believed to be of low quality.

1. The DNA Sample does not match the part sequence or cannot be transformed.

2. The Part is not well documented in the Registry.3. The Part has not been measured.4. Interchangeable parts are not possible.5. Lots of parts are junk.

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Part Quality

Parts in the Registry are believed to be of low quality.1. The DNA Sample does not match the part sequence

or cannot be transformed.– DNA Quality Control Program

2. The Part is not well documented in the Registry.– Curation, Ratings, Judges, Filtering

3. The Part has not been measured.– BioFab, Jason’s measurement program, Devices

4. Interchangeable parts are not possible.– BioLint

5. Lots of parts are junk– Delete, clean up, hide

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BBa_K274002 - email

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BBa_K274002 – Main Page

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BBa_K274002 – Get This Part

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BBa_K274002 - Show 2 other locations

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Extra PstI Site - email

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DNA Samples: Quality Control Program

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Sample QC: Digest Gel

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Sample QC: Antibiotic Test Plate

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Sample QC: Sequence Analysis

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Sample QC: Sample Provenance

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The Registry – Pace of Change

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May 2003

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partsregistry.org

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Example Part

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Parameters, Categories, . . .

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Catalog Style 2009

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Plasmids/Assembly

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2010 DNA Distribution

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3A Assembly

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Sample QC: Shipping Changes

1. Compatible with RFC10 (no EcoRI, XbaI,SpeI, PstI)

2. In pSB1C3 if possible, contact hq@igem.org if not

3. Enter sequencing information

4. Use shipping form

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Part Documentation – Not Good

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Part Documentation – Vanillin p. 1

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Part Documentation – Vanillin p. 2

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Part Documentation – E0040 p. 1

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Part Documentation – E0040 p. 2

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Part Documentation – Why a Wiki

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Part Documentation – Why a Wiki

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Part Documentation – Why a Wiki

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Part Documentation – Why a Wiki

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Devices: A ‘Black Box’

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Devices: Interfaces

Primary InterfacesThe intended functions of this device.

Secondary InterfacesMaterials required for the proper operation of this partor expected to be generated by this part. E.g. energy, waste

Tertiary InterfacesPossible but unexpected interactions with the environment.

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Devices: Main Page

This device takes inputs and makes outputs according the proof of Fremat’s Last Theorem described in our team’s wiki. We ran out of time to complete the proof, but it is obvious to any capable undergraduate.

Other applications of this device include universal cryptography, X-ray vision processing, and world peace.

Pin Name I/O Type Subtype

A Gate Input PoPS URL:alllsdf.asdf.

B Number Input PoPS URL:allsdf.asfd

C Ready Input IPTG URL:rsbp.42356

D Reset Input Heat URL:rsbp.5900

E Result Outpur PoPS URL:alilsdf.asdf

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Devices: Design

This device consists of 3 different parts to compute magic numberskj kjlaalklkjf jaksalskdfj df f f as df f a sd f asd fad f asd f a sdf a df a sd f asd fad sf asdf asdf as df asdf as dfa dsf a sdf as dfas dfaksdjfklkrtf wt 5givi g hio ytf jopuiguyf iuhjii y uuhjoo jo hygyhijk oh ugy t rt y ii I I yt tg h jk I iuy f g hj k I y e 3 4 u jm k hf gh j

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Devices: Other Interfaces

− Examples include proteins used internal to the function of the part.

− Sensitivities to DNA binding proteins− Required use of energy molecules

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Devices: DNA Implementation

DNA Segments

A

B

C

D

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Devices: Representations

SBML Model

<kjdfjl>lksdjflL<<Lkjflds><PART>klsdjflak

Clotho

Lkjfaiovunenzvncvnnn.vzvrvb cwkernfc fyhnkufhabcbxteqwxmc,vgbl,ih0upyt;lfdsnzgoi

Empty

Empty

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Devices: Measurement

− Measurement values− Units (URI)− Measurement Protocol (URI)− Group (URI)− Measurement Batch ID (URI)− Comments

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Devices: References

−References

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More Registries – A Web of Registries

MIT

iGEM in AsiaiGEM in Europe

SB CorpASM

SynBERC

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Registry Version 4

Objects

Tools

MediaWikiEngine

Hard Information

Wiki

Users

mySQL

mySQL

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A 21st Century Registry Design

Syn-Bio-Co 1 Syn-Bio-Co 2 Public Data School 1 Lab 1

ToolTool

Tool Tool

ToolViewer

ViewerViewer

How can the interfaces be developed?

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External Tools

ERC MeetingSynBERC Introduction

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Key Issues

− Getting Synthetic Biologists to add parts

− Quality of the collection

− Intellectual Property

− Thousands of users – live

− Timing

− Integration with bioinformatics tools

− Secrecy and limited access ?

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Some Issues

− How will the interfaces be developed?− Who gets to edit what?− Are there groups, user accounts, a user

community?− Where does the software run? in the user’s PC, in

the lab server, at a central site, in the “cloud” (at Google or Amazon)

− How will pre-publication be handled?− Why will anyone share anything?− Will the core be a community or centralized

development?− How will free-form content be supported?

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Status of Synthetic Biology - 2010

− Science, Engineering, and Industry – Cultures and Values

− Arguments by analogy fail four times, why bother?− Failure to execute vs Failure to imagine− Representation in a young field− Community− 1850 vs 2010:

– Resistors, Capacitors, Inductors, Current Sources, Voltage Sources, Diodes, Transistors, Meters, Shielding, Ground Planes

− Support− Centers for Systems and Synthetic Biology

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Engineering Products– Apple Quadra 840AV

“Ahead of its time, the 840AV and its relative, the Centris/Quadra 660AV, were the first Macintoshes to include 16-bit 48KHz stereo audio recording capability, as well as S-Video and Composite video input and output. They were also the first personal computers that supported speech recognition (PlainTalk) out-of-the-box.”

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Voltmeter - Electronic

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Voltmeter - Microbiology

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Biologists Use - Jello ?

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Good News - Soldering ~ Assembly

BioBrick Standard Assembly - BioBrick Standard Assembly - TKTK

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Good News – Modularity Exists

434 cIRBS T

LacI

LacI

CI

OLac

CI

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Biological Insulation ?

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Apple QuickTake – too early

Apple QuickTake 100 introduced February 16, 1994, the Apple QuickTake 100 was one of the first consumer digital cameras. It came with a heafty price tag of $749 for a single focal length, fixed focus camera with maximum 640 x 480 resolution. Adjusted for inflation the price was nearly $1,100 in 2006 dollars. Shutter sppeds were 1/30 to 1/175 second. The QuickTake 100 could only be used directly with an Apple Mac. The later Quicktake 150, introduced May 1995, could also be used with a Windows PC. Both had only 1mb internal storage and no external storage. They could hold about 16 images before you had to download the images to the computer. Connection to the computer was with a round Apple serial cord. The QuickTake 100 and 150 were made by Kodak.

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iPad 1992 - way too early

Apple PenLite (ATG 1992)

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iGEM 2009

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IAP

2004

2005

2006

2007

2008

2009

2010

2011

2012

4

5

13

32

54

84

112

130

180

250

20

70

120

360

570

825

1100

1300

1800

2500

20

70

150

400

750

1180

1650

1950

2700

3700

Year Teams Jamboree Total

iGEM Growth and Scale

iGEM Scale and Growth

Or Not !

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Heidelberg 2008