SynBERC Site Review

1
Building a computer from off-the-shelf parts
Needs System to write documents, spreadsheets
and communicate
Technology Integration
Computer

Design Integrated system requirements
Assemble from standard, off-the-shelf parts
Technology Base
Op. System
Processors
Dell, IBM, HP, Toshiba
Hard drive
Sound card
Chassis
Parts from any vendor open source software
Software
2
Building a computer from off-the-shelf parts
Technology Base
Op. System
Motherboard
Hard drive
Dell, IBM, HP, Toshiba
Devices from any vendor open source software
Sound card
Chassis
Software

Knowledge base interdependencies
Parts/devices/chasses requirements
Fundamental knowledge to build basic computer
components
Knowledge Base
Other technologies cell phone
Characterization
Silicon wafer
High-level lang.
Standard connections
Independent devices
Foundational science and applied research
3
Taxol
4
Synthesis of Taxol
Needs Chemical plant to synthesize taxol
Technology Integration
Taxol synthesis plant

Design Integrated system requirements
Assemble from standard, off-the-shelf parts
Technology Base
Other parts of the plant vendors
Pipes
Evaporators
Distillation
Reactors
Control system
Other unit ops
Purchase unit operations from other areas of the
plant
5
Synthesis of Taxol
Technology Base
Other parts of the plant vendors
Pipes
Evaporators
Distillation
Purchase unit operations from other areas of
the plant
Reactors
Control system
Other unit ops

Knowledge base interdependencies
Requirements to integrate unit operations
Fundamental knowledge to build basic unit
operations
Knowledge Base
Chemistry
6
Chemical synthesis of taxol
7
Synthesis of Taxol
Technology Base
Other parts of the plant vendors
Pipes
Evaporators
Distillation
Reactors
Control system
Other unit ops
Purchase unit operations from other areas of
the plant

Knowledge base interdependencies
Requirements to integrate unit operations
Fundamental knowledge to build basic unit
operations
Knowledge Base
Chemistry
Kinetics Reactor design
8
Designing and building parts Parts Engineering
9
Synthesis of Taxol
Other parts of the plant vendors
Pipes
Evaporators
Distillation
Purchase unit operations from other areas of
the plant
Reactors
Control system
Other unit ops

Knowledge base interdependencies
Requirements to integrate unit operations
Fundamental knowledge to build basic unit
operations
Knowledge Base
Process design
Chemistry
Mass transfer
Standards
Kinetics Reactor design
10
Standard interfaces between parts
11
Synthesis of Taxol
Other parts of the plant vendors
Pipes
Evaporators
Distillation
Purchase unit operations from other areas of
the plant
Reactors
Control system
Other unit ops

Knowledge base interdependencies
Requirements to integrate unit operations
Fundamental knowledge to build basic unit
operations
Knowledge Base
Construct other unit operations
Process design
Chemistry
Mass transfer
Standards
Kinetics Reactor design
Other engineering disciplines mechanical
engineering
12
Building a Taxol-synthesizing microorganism
13
Synthesis of Taxol
Needs Synthesis of taxol in a microbe
Technology Integration
Drug-producing microbe

Design Integrated system requirements
Assemble from standard, off-the-shelf parts
Technology Base
Genes
Enzymes
14
Building a Taxol-synthesizing microorganism
biosynthesis pathways
15
Synthesis of Taxol
Needs Synthesis of taxol in a microbe
Technology Integration
Drug-producing microbe

Design Integrated system requirements
Assemble from standard, off-the-shelf parts
Technology Base
Describe parts in papers
Plasmids
Gen. control
Genes
Enzymes
Host
rDNA technol.
Request parts or hosts from your colleagues or
competitors
16
Synthesis of Taxol
Technology Base
Plasmids
Gen. control
Genes
Enzymes
Host
rDNA technol.

Knowledge base interdependencies
Requirements to integrate parts, devices, and
hosts
Fundamental knowledge to build biological parts,
devices, and hosts ????
Knowledge Base
Biochemistry
Design????
Gen. con.??
Standards????
Genetics
Biological Engineering
17
Constructing a Taxol-producing, tumor-seeking
microorganism
Needs Tumor-hunting microbe
Technology Integration
Drug-producing microbe

Design Integrated system requirements
Assemble from standard, off-the-shelf parts
Technology Base
Sign. trans.
Gen. control
Recognition
Enzymes
Host
Swarm cont.
18
Other applications of engineered biological
systems

• Information processing
• Energy production
• Chemical processing
• Materials fabrication
• Environmental sensing and remediation
• Human diagnostics and therapeutics

19
The challenges in engineering biology

• Biological engineering has long development times
  due to the lack of useful tools to reprogram
  living systems
• Most biological parts were developed long ago
  and/or without an engineering viewpoint
• Natural biological parts and devices often have
  multiple interactions with other parts/devices in
  the cell
• Biological parts have no IEEE-equivalent standard
  for connections
• Many of the good biological parts require
  expensive royalty payments

20
Synthetic Biology

• How is this different from genetic engineering?
• Development of foundational technologies that
  make it easier to engineer biology.
• Design and construction of core components that
  can be used in combination reliably
• Tools for hiding information and managing
  complexity from DNA to low-level parts to
  devices, systems, and applications

21
Past lessons from engineering

• Transition of physics to electrical engineering
• Transition of chemistry to chemical engineering
• Transition of mechanical crafts to mechanical
  engineering
• And so on
• Synthetic biology will learn lessons from all of
  these paradigms.

22
Knowledge base that has enabled other areas of
engineering

• Abstraction
• Design
• Composability
• Characterization
• Standardization

23
Knowledge base to enable synthetic biology
Technology Base
Registry, Open Source
Chasses
Parts
Existing parts/devices/ chasses
Devices

Parts/devices/chasses requirements
Knowledge base interdependencies
Fundamental knowledge to build basic
parts/tools/chasses.
Knowledge Base
Abstraction

• Abstraction
• Insulate relevant characteristics from
  overwhelming detail
• Simple artifacts that can be used in combination

24
Knowledge BaseAbstraction
Systems
Devices
Parts
25
Knowledge BaseAbstraction
Systems
Devices
Parts
26
Knowledge base to enable synthetic biology
Technology Base
Registry, Open Source
Chasses
Parts
Existing parts/devices/ chasses
Devices

Parts/devices/chasses requirements
Knowledge base interdependencies
Fundamental knowledge to build basic
parts/tools/chasses.
Knowledge Base
Design
Abstraction

• Design
• Models/computer algorithms for the design of new
  parts/devices
• Automation of design algorithms user specified
  parts

27
Knowledge BaseDesign

• Models/computer algorithms for the design of new
  parts/devices
• Tunable interfaces affinity modulation
• Orthogonal interfaces
• Assembly interfaces scaffolds
• New catalytic function sequence libraries for
  directed evolution
• Automation of design algorithms user specified
  parts

Engineered Novel Protein interface
Designing Orthogonality
New DNA specificity
28
Knowledge base to enable synthetic biology
Technology Base
Registry, Open Source
Chasses
Parts
Existing parts/devices/ chasses
Devices

Parts/devices/chasses requirements
Knowledge base interdependencies
Fundamental knowledge to build basic
parts/tools/chasses.
Knowledge Base
Design
Composability
Abstraction

• Composability
• Rules insulating design process from details of
  fabrication
• Enable parts, device, and system designers to
  work together

29
Knowledge BaseComposability

• Rules insulating design process from details of
  fabrication
• Enable parts, device, and system designers to
  work together

LacI
cI
? cI-857
OLac
RBS
T
30
Knowledge base to enable synthetic biology
Technology Base
Registry, Open Source
Chasses
Parts
Existing parts/devices/ chasses
Devices

Parts/devices/chasses requirements
Knowledge base interdependencies
Fundamental knowledge to build basic
parts/tools/chasses.
Knowledge Base
Design
Composability
Characterization
Abstraction

• Characterization
• Input-output characteristics of existing and new
  parts/devices

31
Knowledge BaseCharacterization

• Input-output characteristics of existing and new
  parts/devices

Tet Repressor
Lac Repressor
32
Knowledge base to enable synthetic biology
Technology Base
Registry, Open Source
Chasses
Parts
Existing parts/devices/ chasses
Devices

Parts/devices/chasses requirements
Knowledge base interdependencies
Fundamental knowledge to build basic
parts/tools/chasses.
Knowledge Base
Design
Composability
Characterization
Standardization
Abstraction

• Standardization
• Physical Connections
• Functional connections
• Performance

Enabling off-the-shelf use
33
Knowledge BaseStandardization
34
Knowledge BaseStandardization

• Physical Connections
• Functional connections
• Performance

35
Knowledge base to enable synthetic biology
Technology Base
Registry, Open Source
Chasses
Parts
Existing parts/devices/ chasses
Devices

Parts/devices/chasses requirements
Knowledge base interdependencies
Fundamental knowledge to build basic
parts/devices/chasses.
Knowledge Base
Other users
Design
Composability
Characterization
Standardization
Abstraction
Other resources

• Inputs from others, Outputs to others (e.g.,
  measurement)
• Request for measurement (e.g., how do you measure
  POPs?)