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Synthetic Biology and iGEM

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a new and rapidly emerging discipline that aims at the (re-)design and ... Fabricate materials and structures. Produce energy. Provide food. Process information ... – PowerPoint PPT presentation

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Title: Synthetic Biology and iGEM


1
Synthetic Biology and iGEM
  • Cambridge iGEM2007 team
  • 27 July 2007

2
Synthetic Biology
  • '...a new and rapidly emerging discipline that
    aims at the (re-)design and construction of (new)
    biological systems.' Synthetic Biology 3.0

3
Synthetic Biology
  • 'Combines science and engineering in order to
    design and build novel biological functions and
    systems.' Wikipedia


4
Synthetic Biology
  • AN ENGINEERING PERSPECTIVE
  • Engineers view biology as a technology
  • Heavy emphasis on developing foundational
    technologies
  • International Genetically Engineered Machine
    competition (iGEM)?
  • Registry of Standard Biological Parts

5
iGEM
  • "Can simple biological systems be built from
    standard, interchangeable parts and operated in
    living cells? Or is biology just too complicated
    to be engineered in this way?" Randy Rettberg,
    Director of the iGEM competition

'Dunno. Let's try to build some devices...'
6
iGEM BioBricks
  • Library of standardized parts (called BioBrick
    standard biological parts)?
  • Use them
  • Design your own
  • Contribute to the registry

B0034
RBS
7
iGEM The Registry
8
iGEM
  • BROADER GOALS
  • Enable systematic engineering of biology
  • Promote the open and transparent development of
    tools for engineering biology
  • Help construct a society that can productively
    apply biological technology

9
Synthetic Biology
  • ENGINEERED BIOLOGICAL SYSTEMS
  • Maintain and enhance human health and our
    environment
  • Fabricate materials and structures
  • Produce energy
  • Provide food
  • Process information

10
Synthetic Biology
  • POTENTIAL APPLICATIONS Health
  • Sepsis - An overwhelming systemic immune response
    to toxin-producing bacteria in the bloodstream
  • Designed feedback loop
  • Inhibits signaling cascade at MyD88 (a 'weak
    spot')?
  • 26 new BioBricks
  • Type of artificial immunotolerance

11
Synthetic Biology
  • POTENTIAL APPLICATIONS Materials Information
    Processing

12
Synthetic Biology
  • POTENTIAL APPLICATIONS Energy
  • Carbon sequestration
  • Bacteria-produced ethanol
  • Bacteria hydrogen production

13
Our Team
  • A mix of biologists, engineers and physicist.
  • Shared enthusiasm of synthetic biology

Front row, from left Narin Hengrung, Yi Han,
David Wyatt Second row, from left Zhizhen Zhao
(Jane), Stefan Milde, Dmitry Malyshev, Xinxuan
Soh (Sheila) Third row, from left Yi Jin Liew,
John Crowe, Lovelace Soirez, Stephanie May, Yue
Miao Back row, from left James Brown (PhD
student mentor), Jim Haseloff (faculty), Gos
Micklem (faculty)
14
Our Ideas
  • Gram Positive bacteria, B. subtilis
  • Signallingtwo-component peptide signalling
    system
  • Bacterial Amplifier


15
B. subtilis General background
  • Gram-positive soil bacterium
  • Genome 4100 genes
  • Class I contaminant
  • Often used as a model Gram-Positive organism
  • Codon usage differs from E. coli

16
Why use B. subtilis?
  • Model Gram-positive organism, not yet used in
    iGEM
  • Better at secreting substances than Gram-negative
    bacteria
  • Easy to transform
  • Adds new biobricks and new capabilities to
    Registry

17
Our aims
  • Culturing B. subtilis
  • Transformation methods
  • Promoters and shuttle vectors
  • Assembling a system

18
The agr system of S. aureus
  • Oligopeptide-based quorum sensing

AIP
AgrC
AgrB
membrane
P
AgrA
P2 promoter
agrB
agrA
agrC
agrD
19
Peptide signalling importance
  • Bacterial Maze
  • Another independent signalling system for the
    Registry
  • and a paradigm for more?
  • Aid to research into S. aureus countermeasures

20
Peptide signalling roadmap
  • Transfer agr system into B. subtilis, then into
    E. coli

B. subtilis biobrick chassis
Senders and receivers in B. subtilis
Natural agr operon
AIP sender device
AIP receiver device
Senders and receivers in E. coli
Mutant fepA gene
Permeability device
21
Biological Amplifier
  • To build a standard amplifier which can be used
    in any synthetic (biobricked) system
  • It should take a standard PoPS input and give a
    standard PoPS output

22
Biological Amplifier
  • Amplifier construct

23
Biological Amplifier Further uses
  • Repressor
  • Signal divider

24
Biological Amplifier Further uses
  • Logic gates XOR

25
Biological Amplifier Further uses
  • Logic gates AND

Promoter 1
Activator 1
Activator 3
PoPS 1
Promoter 3
PoPS 3
Promoter 2
Activator 2
Activator 3
PoPS 2
26
Biological Amplifier
  • Overall this system could be widely used within
    synthetic biology given its flexibility and the
    range of possible basic constructs

27
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