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SYNBIOLOGY - An Analysis of Synthetic Biology
Research in Europe and North America
4,5/4,5 CM 4,5/4,5 CM 4,5/4,5 CM 4,5/4,5 CM
SYNBIOLOGY: SYNBIOLOGY: An Analysis of Synthetic An Analysis of Synthetic Biology Research in Europe and North AmericaBiology Research in Europe and North America
Definition of Synthetic Biology ActivitiesDefinition of Synthetic Biology Activities
30th May 200630th May 2006
European Commission, BrusselsEuropean Commission, Brussels
SYNBIOLOGY
Brussels, 30 May 2006
Introduction (1)
Definition of Synthetic Biology Activities
- 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
SYNBIOLOGY
Brussels, 30 May 2006
Definition of Synthetic Biology Activities
- 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
Introduction (2)
SYNBIOLOGY
Brussels, 30 May 2006
Integrity of the Basic Genetic
System
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
Genetic Engineering & Metabolic EngineeringConsecutive Substitution or Expansion of Natural Function
General Recombinant DNA Technologies focus on„Metabolic Engineering“
Continuousincrease of complexity
Affecting the integrity of the basic genetic system
->Use of not natural nucleotides as artificial genetic information store and
-> use of not triplet codons
System Integration „de novo“ – ApproachProf. Norman Packard Group, Prof. Mark A. Bedau
Proto Life SRL – Los Alamos Bug - PACE
Cellular Differentiation &Mitotic Engineering
Éngineering
„Bottom Up“ – Approach
„Top Down“ - Approach
Signal Transduction Éngineering
Creation of newartificial genetic
system
Synthetic Biology
Artificial Biology
Definition of Synthetic Biology Activities
SYNBIOLOGY
Brussels, 30 May 2006
Differentiation by type of genetic element : Gene Regulatory Circuits are composed of different genetic functions : regulating function (regulators) versus regulated function
Regulated Gene Functions for
• Biocatalysis (Enzymes, Ribozymes)
• Structure Formation ((Glyco)proteins, RNA)
• Biosensing (Proteins)
• Regulators• Catalysts• Structural Elements• Sensors
Signal Sensors
Signal Input Parameters
Signal Processing
Signal Integration
Output Parameters
Actuator/ Signal/ Productin vitroin vivo
ex vivo
in silico
Regulating Gene Functions in CIS or TRANS : Regulation of Regulatory Elements by
• Regulation of Proliferation
• Regulation of Cellular Differentiation
• Regulation Chemical Differentiation
Definition of Synthetic Biology Activities
SYNBIOLOGY
Brussels, 30 May 2006
Development Stages
Definition of Synthetic Biology Activities
- 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)
SYNBIOLOGY
Brussels, 30 May 2006
Class III Synthetic Biology Activities (SB3)
Definition of Synthetic Biology Activities
- 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
SYNBIOLOGY
Brussels, 30 May 2006
Class II Synthetic Biology Activities (SB2)
Definition of Synthetic Biology Activities
- 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
SYNBIOLOGY
Brussels, 30 May 2006
Class I Synthetic Biology Activities (SB1)
Definition of Synthetic Biology Activities
- 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
SYNBIOLOGY
Brussels, 30 May 2006
Class I Synthetic Biology Activities (SB1)
Definition of Synthetic Biology Activities
- 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
SYNBIOLOGY
Brussels, 30 May 2006
in vivo
Synthetic Biology
in silico
SB Structural
in vivo
Synthetic Biology
in silico
SB Systemic
in vitro
Synthetic Biology
in silico
SB Theory
general Bioinformatics
Systems Biology
system oriented Bioinformatics
Structural Bioinformatics
classical Genomics
functional Genomics
in silico Genomics
structural Genomics
Synthetic Biology 1 (SB1) : Artificial Systems Functional Devices Artificial Standard Parts
Synthetic Biology 2 (SB2) : Systems ------------ Modified Natural Parts
Synthetic Biology 3 (SB3) : Natural and
slightly modified natural Parts
SB1 - Transition Point :
mixed Systems natural and artificial parts generating mixed devices
Artificial devices of standardized functional behaviour is the unique feature of SB1
SB1 - Transition Point :
simple artificial arrangements of natural parts generating simple artificial systems
All Artificial
All Natural
SB2 – Transition Point : Complex artificial arrangements of natural and slightly modified natural parts generating simple individual systems
Definition of Synthetic Biology Activities
Specific Functional
Interactions on the
Structural Level
At least a Minimum of
two Designed
Functional Interactions
SYNBIOLOGY
Brussels, 30 May 2006
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, 438:449-453
SB1 - Parts, Devices and Systems
• Standardisation• Decoupling (Design & DNA-Synthesis)• Abstraction (circuitry design models, simulation, improvement)• Evolution
Definition of Synthetic Biology Activities
SYNBIOLOGY
Brussels, 30 May 2006
Synthetic Biology Aspects of Scope
• Only in vivo SB ? -> 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
- adressed at the SB2.0 Conference - adressed at the SB2.0 Conference
Definition of Synthetic Biology Activities
Conclusions : Answers to Questions Raised during Synbiology Project
SYNBIOLOGY
Brussels, 30 May 2006
Definition of Synthetic Biology Activities
Examples for Synthetic Biology - DesignExamples for Synthetic Biology - Design
Files :Files :
(1) SB-design.pdf(1) SB-design.pdf
(2) omnibus.uni-freiburg.de.pdf (2) omnibus.uni-freiburg.de.pdf
by Andrey Kuznetsovby Andrey Kuznetsov
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