Applications of synthetic biology

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Applications of synthetic biology Philipp
Holliger, PhD MRC Laboratory of Molecular Biology
You see things and you say Why? But I dream
things that never were And say Why not? G. B.
Shaw, Back to Methusalem
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What can synthetic biology do?

• Bricks Mortar gene synthesis, genome
  sequencing
• Reprogramming cellular behaviour
• sensors, switches etc.
• Drug synthesis
• Expanding the chemistry of life / Nanotechnology
• - Redesigning life
• - top down
• - bottom up

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High-throughput DNA synthesis sequencing
Foster Church (2007) Genome Res, 17, 1
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Sequencing synthesis follow Moores law
Human genome sequence (2001) 10 yrs, 3 billion
/ (2007) 2 months 2 million Total synthesis of
bacterial genome (2008)
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Building a toggle switch
Cellular memory
Gardner et al (2000) Nature, 403, 339 Kobayashi
et al (2004) PNAS, 101, 8414
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Bacterial photography
Synechosystis Photoreceptor, Phytochrome
synthesis genes (ho1, pcyA) E. coli osmotic
shock response circuit (ompC), ?-galactosidase
Levskaya et al (2005) Nature, 438, 441
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Building a sender receiver
Basu et al (2005) Nature, 434, 1130
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Towards biobots cancer invading bacteria
Vibrio fisheri Quorum sensing (cell density
sensing) E.coli hypoxia responsive promotor
(fdhF) Yersinia pseudotuberculosis invasin (inv)
Anderson et al (2006) J Mol Biol, 355, 619
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Building bacterial drug factories
Sweet wormwood (Artemisia annua)
Martin et al (2003) Nature Biotechnol, 21, 796 Ro
et al (2006) Nature, 440, 940
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A hierarchy of functional units
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Orthogonality unfreezing the genetic code
Amino acid 1
New Amino acid 2
tRNA synthetase 1
tRNA synthetase 2
tRNA 2
tRNA 1
Synthesis of proteins with unnatural amino acids
Insert pathway Bacterium with expanded chemistry
Wang et al (2001) Science,292, 498
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Orthogonal kinase substrates
Blethrow et al (2008) PNAS 105, 1442
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Redesigning life top down Minimal genome project
Not all genes are essential for life
Mycoplasma genitalium 482 genes, 382 essential
E.coli 15 genome reduction (remove
transposons, mobile genetic elements) -gt more
stable host
Glass et al (2005) PNAS 103, 425 Posfai et al
(2006) Science, 312, 1044
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Directed evolution
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Ghadessy et al (2001) PNAS 98, 4552
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DNA nanotechnology using DNA to arrange
nano-objects in space time
DNA origami
DNA walker
DNA cube
Replicatable octahedron
DNA tiles
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Redesigning life bottom up
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What can synthetic biology deliver ( in 5-10
years time)?
What is life?
Nanotechnology Material science
biomolecules / organisms with expanded chemistry
de novo design and synthesis of tailor-made
organisms
New drugs
Smart therapeutics
biosynthesis / degradation of complex chemicals
pharmaceuticals
programmable biological systems biobots
Bioremediation
Tissue regeneration
Biofuels