SYNBIOLOGY - An Analysis of Synthetic Biology

Research in Europe and North America

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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