Title: SYNBIOLOGY: An Analysis of Synthetic Biology Research in Europe and North America
1SYNBIOLOGY An Analysis of Synthetic Biology
Research in Europe and North America Definition
of Synthetic Biology Activities 30th May
2006 European Commission, Brussels
2Definition 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
3Definition 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
4Definition 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
5Definition 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
6Definition 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)
7Definition 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
8Definition 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
9Definition 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
10Definition 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
11Definition 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
12Definition 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
13Definition 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
14Definition of Synthetic Biology Activities
Examples for Synthetic Biology - Design Files
(1) SB-design.pdf (2) omnibus.uni-freiburg.de.pdf
by Andrey Kuznetsov