SYNBIOLOGY: An Analysis of Synthetic Biology Research in Europe and North America

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SYNBIOLOGY An Analysis of Synthetic Biology
Research in Europe and North America Definition
of Synthetic Biology Activities 30th May
2006 European Commission, Brussels
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Definition of Synthetic Biology Activities
Introduction (1)

• Synbiology project provided discussion and
  structuring of synthetic biology activities in
  Analysis of Synthetic Biology Literature and
  Statistical Review
• No single agreed definition on synthetic biology
  activities
• Definition provided by NEST High-Level Expert
  Group (2006)
• Synopsis will be provided in upcoming paper
• Consensus Synthetic Biology - a Structured View

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Definition of Synthetic Biology Activities
Introduction (2)

• Synthetic biology represents missing
  interdisciplinary links from molecular biology to
  engineering technologies close to IT and advanced
  nano-technology sciences
• Synthetic biology application potential is
  enormous and universal to all life science based
  industries
• As well as other industries for improving
  processes and generating totally new products and
  services

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Definition of Synthetic Biology Activities
Top Down - Approach
Synthetic Biology
Artificial Biology
System Integration de novo Approach Prof.
Norman Packard Group, Prof. Mark A. Bedau Proto
Life SRL Los Alamos Bug - PACE
RNA-World Cellular Systems Szostack
Group Minimal Cell Project Piere Luigi Luisi
Group Intermediate Up - Approach Reduction of
Natural on Basic Function Graig Venter Group
Affecting the integrity of the basic genetic
system -gtUse of not natural nucleotides as
artificial genetic information store and -gt use
of not triplet codons
Creation of new artificial genetic system
Integrity of the Basic Genetic
System
Cellular Differentiation Mitotic Engineering
Éngineering
Signal Transduction Éngineering
Genetic Engineering Metabolic
Engineering Consecutive Substitution or Expansion
of Natural Function General Recombinant DNA
Technologies focus on Metabolic Engineering
Continuous increase of complexity
Bottom Up Approach
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Definition of Synthetic Biology Activities
Differentiation by type of genetic element
Gene Regulatory Circuits are composed of
different genetic functions regulating
function (regulators) versus regulated function

• Regulating Gene Functions in CIS or TRANS
  Regulation of Regulatory Elements by
• Regulation of Proliferation
• Regulation of Cellular Differentiation
• Regulation Chemical Differentiation

• Regulated Gene Functions for
• Biocatalysis (Enzymes, Ribozymes)
• Structure Formation ((Glyco)proteins, RNA)
• Biosensing (Proteins)

• Regulators
• Catalysts
• Structural Elements
• Sensors

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Definition of Synthetic Biology Activities
Development Stages

• Three developmental stages of synthetic biology
  can be identified
• Mainly influenced by steadily increasing
  technical feasibilities of enabling technologies
  - the basis for generating a general trend to
  more complex system oriented thinking.
• These stages of can be described as shifts in
  paradigm
• Class III Synthetic Biology Activities (SB3)
• Class II Synthetic Biology Activities (SB2)
• Class I Synthetic Biology Activities (SB1)

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Definition of Synthetic Biology Activities
Class III Synthetic Biology Activities (SB3)

• Synthetic biology as an expression of early
  genetic engineering experiments mainly focused on
  in vivo synthetic biology
• Simple and individual modifications of natural
  function (e.g. improvement of a promoter)
  performed on natural genetic parts without
  standardization
• Aimed at single functional improvements for
  bio-production in mostly heterogenious expression
  rather than generation of functional defective
  mutations of DNA constructions for unraveling
  genetic function

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Definition of Synthetic Biology Activities
Class II Synthetic Biology Activities (SB2)

• Intentional design of systemic functional
  interactions of new assemblies genes and its
  products and appropriate regulatory circuits
• Such as in Biochemical Pathway Designs consisting
  of new configurations of regulators and regulated
  parts like sensors, catalysts and structural
  elements
• Mixing natural genetic elements, artificially
  modified by rational designed or evolved by
  molecular breeding
• Mosaics of natural and partially designed parts

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Definition of Synthetic Biology Activities
Class I Synthetic Biology Activities (SB1)

• Artificial designs of genetic circuits and
  pathways using only rational engineered or
  evolved standardized parts which meet technical
  requirement specifications.
• Will be used for future artificial regulation,
  catalysis, structural parts
• Or for sensing in vivo or for biobased
  nano-technology applications in vitro synthetic
  biology (nanowires, biocomputing, bioelectronics,
  self-assembly), artificial biology and artificial
  life

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Definition of Synthetic Biology Activities
Class I Synthetic Biology Activities (SB1)

• New Paradigm Drew Endy (2005) Artificial
  Synthetic Biology molecular parts of biological
  function and devices of higher functional order
  built thereof have some mandatory features of
  proven quality which are necessary to assure its
  function in vivo as well as in vitro
• Should be compatible with defined interfaces to
  other parts with defined robust function showing
  reproducible behavior
• Ideally the function can be established
  independently of the host system
• Excellent documentation and standardisation of
  parts are prerequisites

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Definition of Synthetic Biology Activities
Artificial devices of standardized functional
behaviour is the unique feature of SB1
Synthetic Biology 1 (SB1)
Artificial Systems Functional
Devices Artificial Standard Parts
All Artificial
SB1 - Transition Point mixed Systems natural
and artificial parts generating mixed devices
Synthetic Biology 2 (SB2) Systems
------------ Modified Natural
Parts
SB2 Transition Point Complex artificial
arrangements of natural and slightly modified
natural parts generating simple individual systems
Synthetic Biology 3 (SB3) Natural
and slightly modified
natural Parts
in vitro Synthetic Biology
Specific Functional Interactions on the
Structural Level
SB1 - Transition Point simple artificial
arrangements of natural parts generating simple
artificial systems
in vivo Synthetic Biology
in vivo Synthetic Biology
At least a Minimum of two Designed Functional
Interactions
in silico SB Structural
in silico SB Systemic
in silico SB Theory
All Natural
general Bioinformatics
Systems Biology
system oriented Bioinformatics
Structural Bioinformatics
classical Genomics
functional Genomics
in silico Genomics
structural Genomics
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Definition of Synthetic Biology Activities
SB1 - Parts, Devices and Systems

• Standardisation
• Decoupling (Design DNA-Synthesis)
• Abstraction (circuitry design models,
  simulation, improvement)
• Evolution

• Mandatory features of Synthetic Biology
• molecular parts and devices
• standardized
• compatible
• defined interfaces
• robust reproducible behavior
• well documented
• independent of host system

Devices are small integrated genetic circuits
Functional genetic circuits of regulated parts
with defined behavior/ properties (see
parts) The difference parts will be public
domain, wheras devices will start to be patented
intensive and frequently

• Systems functionally integrated genetic circuit
  systems composed of parts and devices
• extended compatible crosstalking regulator
  parts/ devices networks with defined properties
• net of networks (e.g. regulatory and catalyst,
  metabolic) networks with defined properties

Source Drew Endy (2005) Foundations for
engineering biology, Nature Review, 438449-453
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Definition of Synthetic Biology Activities
Conclusions Answers to Questions Raised during
Synbiology Project
- adressed at the SB2.0 Conference

• Synthetic Biology Aspects of Scope
• Only in vivo SB ? -gt in vitro SB is accepted to
  be SB
• Self organizing molecular systems (DNA RNA
  Proteis, Sugars)
• Biomineralisation (Silicon, Magnetite,
  Hydroxylapatite)
• application of biomolecules in vitro
  (Polyproteins, Biomimetics)
• Only regulation in vivo SB ?
• Clearly not there is a clear focus on
  materials and biobased replicative production
• Only SB1 SB ?
• with few exemptions the applications were at the
  transition point to SB1 and not hard core SB1

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Definition of Synthetic Biology Activities
Examples for Synthetic Biology - Design Files
(1) SB-design.pdf (2) omnibus.uni-freiburg.de.pdf
by Andrey Kuznetsov