A PlatformBased Design Environment for Synthetic Biological Systems

1
A Platform-Based Design Environment for Synthetic
Biological Systems

• Douglas Densmore1, Anne Van Devender2, Matthew
  Johnson1, Nade Sritanyaratana1
• 2009 Richard Tapia Celebration of Diversity in
  Computing Conference
• April 2nd, 2009

• University of California, Berkeley
• Washington and Lee University

2
Outline

• Synthetic Biology Overview
• Standard Parts
• Example Systems
• Opportunities and Challenges
• Platform-Based Design in Synthetic Biology
• PBD Overview and Tool Landscape
• Clotho Overview
• Three example design flows
• Future Plans

3
What is Synthetic Biology?

• Adding multi-gene DNAs into well-characterized
  organisms to understand biological behavior or
  perform useful functions in diverse areas
  including therapeutics, biosensors, bioenergy,
  bioremediation, chemicals, and materials
  production.

Putting the Engineering back in Genetic
Engineering
3. Standards
2. Automated Assembly
1. Abstractions
Automatic Sequencing PCR Recombinant DNA
Drew Endy, Stanford
4
Synthetic Biology Abstraction Overview
Biological Engineering?
Protein Engineering Promoter Engineering
Synthetic Biology
bases
parts
devices
A T C G
genomes
0.5-10Mb
1-20kb
0.1-3kb
1bp
Ribosome Binding Site
Terminators
Regulatory
Reporters
One instance of an inverter
Registry of Standard Biological Parts
http//parts.mit.edu
Actuators
Circuits
Sensors
5
Standardized Parts

• BioBricks (Tom Knight, MIT) one of the most
  prevalent standards.
• 2ab Layered assembly (J. Christopher Anderson) is
  another proposal
• Look to reduce reactions required, increase
  productivity, aid in reliability, and increase
  reuse.

Assembly Vector
Cloning Site
Replication Origin
Antibiotic Resistance
Restriction Sites
Part
6
Example Devices
Davidson-Missouri Western/DNA Encoded XOR Gates
(iGEM 2008)
Need tools to Store, Analyze, and Assemble
systems!
NYMU-Taipei Urea Transporter (iGEM 2008)
More info http//2008.igem.org/Main_Page
7
Synthetic Biology Examples

• Bactoblood UC Berkeley
• A cost-effective red blood cell substitute
  constructed from engineered E. coli bacteria.
  http//parts.mit.edu/igem07/index.php/Berkeley_UC

• Bactricity - Harvard
• Bacterial biosensors with electrical output.
  http//2008.igem.org/TeamHarvard

• BacToKidney NYMU-Taipei
• Bacteria to replace a hemodialysis machine to
  remove toxic waste for treating kidney failure.
  http//2008.igem.org/TeamNYMU-Taipei

8
Design Automation Opportunities
Combinational Logic Design in Synthetic Biology,
Douglas Densmore, J. Christopher Anderson, IEEE
International Symposium on Circuits and Systems
(ISCAS) 2009, Taipei Taiwan, May 2009. (To Appear)
9
Abstractions Difficulties
10
Current Design Environment
Multiple Tools
Tool 1
Data Model Support?
Communication Issues
Exists? Proprietary?
Tool N
Iterative
Global Repository
Manual
Starting Design
Multiple Files
Lab Database
Lab 1
Access Issues
Lab N
Standards?
Need An integrated design environment with
flexible database support and a data model with a
meaningful semantic
?
11
iGEM 2008 Winner Best Software Tool and Gold
Medal
J. Christopher Anderson
Berkeley Computational iGEM Team Nade
Sritanyaratana, Ann Van Devender, Matthew Johnson
12
What is Platform-Based Design?
Platform Based Design repeats itself vertically
(fractal nature of design)
Computer Aided Design (CAD) Using a computer to
design something
Spec
Application Instance
Application Space
Electronic Design Automation (EDA) Synopsys,
Cadence, Mentor Graphics
Constraints

• What a design does.
• Functionality separated from implementation

Platform
Behavior
Electronic System Level Design (ESL) SystemC,
System Verilog, Blue Spec
Cost Export
Architectural Space
Platform Instance

• How a design is realized.
• Implementation separated from functionality.

Cost
Platform Based Design (PBD) Polis, Metropolis,
Metro II
Platform Based Design can be applied
horizontally (different domains)
A Platform-Based Design Methodology for the
Electronic System Level, Douglas Densmore,
Abhijit Davare, VDM Verlag, ISBN978-3836473149
13
SynBio Tool Landscape
Computation/Simulation Tools
Tinkercell (UW)
Viz-a-Brick (Davidson-Missouri Western)
BioJADE (UCB)
BioMortar (Waterloo)
Gene Designer (DNA 2.0)
APE (Utah)
BioStudio (Johns Hopkins)
GenoCAD (VTech)
Parts Registry (MIT)
Design/Analysis Tools
Data Management Tools
More info http//biocad-server.eecs.berkeley.edu/
wiki/index.php/Related_Work
14
Clotho Design Environment
Clotho Stats 130 Files, Java 6, Net Beans IDE
15
Design Environment
Clotho Parts Manager
Clotho Sequence View
Clotho Binding Manager
Clotho Algorithm Manager
Clotho Plate Manager
16
Clotho Data Model/Integration
17
Flow 1 New Part Creation
Un-associated data (e.g. new idea)
Associated data (e.g. part of family/collection)
Creation Path
Data Source
Part View and Manipulation
Data Manipulation and Design
Mapping
Storage Path
Flow
Implementation
Clotho Parts Manager
Clotho Sequence View
PoBoL Inspired Internal Data Structure
MIT Registry of Standard Biological Parts

• Organized by Collections
• Hierarchy Based
• BioBrick
• DNA
• Samples

• Sequence Manipulation
• Data Analysis
• ORF
• Feature/Enzyme Highlighting
• Translation, Reverse Comp.
• Part Export/Package

Relational Database (e.g. mySQL)
Clotho Binding Manager
18
Flow 2 Composite Part Creation
Clotho Parts Manager
Collection
Data Source
Part View
Mapping
Display Plug-In
Specific Part
Part Manipulation
Composition Plug-In
Flow
Implementation
EcoRI BglII BamHI Xhol
Biobrick
GAATTCatgAGATCT-Part-GGATCCatgCTCGAG
DNA
Primer Design
Samples
Hierarchy Changes
Clotho Plug-In Framework
19
Flow 3 Physical Part Assembly Flow
Clotho Parts Manager
Data Source
Part Viewer(s)
Algorithm Environment
Mapping
Collection of Theoretical Parts
Flow
Implementation
Clotho Plate Manager
Clotho Algorithm Manager
20
Future Development Plan
Lachesis
2
Moirae
Visualization Infrastructure
Data Management Infrastructure
Analysis Infrastructure
1
Atropos
3
Free well
Basic Part
Composite (Dead)
Composite (Alive)
Assembly Infrastructure
21
Future Development Plan Cont.
Archetype 1 (e.g. Biofuels)
Archetype 2 (e.g. Biosensors)
Archetype 3 (e.g. Therapeutics)
Workflow 3
Workflow 1
Workflow 2
Development of Workflow Description Environment
(WDE)
Connection to Antimony (UW), Kepler (UCB), VOV?
Moirae DL
2 EECS Students
2 BioEng Students
1 EECS Student
Connection to BioJADE (UCB), Tinkercell (UW),
Salis/Voigt (UCSF)?
Visualization and Analysis Development
Connection to Joint BioEnergy Institute (JBEI)
Registry?
Database and Data Model Development
Assembly and Robotic Interface Development
Connection to a variety of robots?
22
More information and thanks

• Thanks to CHESS, SynBERC
• J.Christopher Anderson, Chris Voigt, Josh
  Kittleson, Christopher Batten, Will DeLoache, Tim
  Hsiau, Brian Zimmer, Bing Xia, Roger Tu, Josh
  Kittleson
• http//2008.igem.org/TeamUC_Berkeley_Tools
• http//biocad-server.eecs.berkeley.edu/wiki