Transcript iGEM Goals Past & Future

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Mon 8-May-2006
40 teams * 10 people = $2M / quarter yr
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http://parts.mit.edu/r/parts/partsdb/view.cgi?part_id=5114
The 2004 iGEM poster was synthetic,
but not biological
( an artifact of light sensitive dyes)
Privately rehabilitated in time for 2005
iGEM jamboree & then publication:
Levskaya A, et al. Nature 2005 Nov 24
Synthetic biology:
engineering
E.coli to see light.
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iGEM Goals Past & Future
Cool
Photogenic
Stunts
Basic Enabling
Technologies
Save the World
Projects
Bull’s
eye
A-to-D &
thresholds
Biosensors &
3D fabrication
Biofilm
Cell-CPU
interfaces
Smart materials
A synthetic multicellular system for programmed
pattern formation Basu, et al. Nature 434:1130
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iGEM Goals Past & Future
Enabling Technologies
Secretion
Useful Applications
Bioenergy .
Human compatible bacteria Tumor busting .
Metabolic engineering
Antibiotic manufacture .
Recombinases, telomeres
Gene therapy & counters
New genetic codes
Protein stability, viral
resistance, safety
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Synthetic combinatorics &
selection for secretion
First
Passage
Second
Passage
trp/tyrA pair of genomes shows the best co-growth
Reppas, Lin & Church ;
Shendure et al. Accurate Multiplex Polony 5
Sequencing of an Evolved Bacterial Genome(2005) Science 309:1728
Environmentally controlled invasion of cancer cells
by engineered bacteria. Anderson et al. J Mol Biol. 2006
Optical imaging: bacteria, viruses, and mammalian cells encoding lightemitting proteins reveal the locations of primary tumors & metastases
in animals. Yu, et al. Anal. Bioanal. Chem. 2003.
accumulate in tumors at ratios in excess of 1000:1 compared with normal
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tissues. http://www.vionpharm.com/tapet_virulence.html
LPS- Capsule+ Dap- for safety
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Engineering a mevalonate pathway in Escherichia coli for
production of terpenoids. Martin VJ, et al. Nat. Biotech 2003
Production of the antimalarial drug precursor artemisinic
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acid in engineered yeast. Ro DK, et al. Nature. 2006
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Programmable ligand-controlled riboregulators
of eukaryotic gene expression.
OFF
ON
ON
Bayer & Smolke 2005 Nature Biotech.
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Combinatorial characterization
P1-GFP-RegP2-RiboRegCR-Output-AA-Stop-Term-P3-RiboRegTA.
50 900 50 25 900 30 3 25 50 90 bp
1 1 10 10 6 10 1 1 10 1E3 # combinations (= 6E8 total)
This gives analog logic (P2, P3 & riboreg) which can be
characterized in situ to quasi-automatically produce pages for a parts
properties handbook.
RegP2,P3: lac, tet, ara, heat, cold, cell-cycle, light(2), quorum, hypoxia(3)
RiboRegCR: cis-regulator: non-cross-reacting 5 types * two strengths.
RiboRegTA: Smolke, Isaacs -- Explore variations on the tiny ligand-specifying region.
Output: Ds-Red, cat, kan, luciferase, tetR, RiboReg2, biosynthetic enzyme
AA: nil, lite, Flag, his-tag, PKS-association, leu-zipper
BBa_R0053 BBa_B0030 BBa_E0040 BBa_B0011 BBa_I0500 BBa_J01010
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Combinatorial Synthesis of
Genetic Networks
Guet et al. Science 2002
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Combinatorial Synthesis of
Genetic Networks
Guet et al. Science 2002
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Nutriceuticals & cosmetics
The FDA does not require disclosure of color or flavor additives if
GRAS ("generally recognized as safe"). A natural flavor is not
necessarily more healthful or purer than an artificial one. When
almond flavor -- benzaldehyde -- is derived from natural sources, such
as peach and apricot pits, it contains traces of hydrogen cyanide, a
deadly poison. Benzaldehyde derived by mixing oil of clove and amyl
acetate does not contain any cyanide. Nevertheless, it is legally
considered an artificial flavor and sells at a much lower price.
Feb 2005 the FDA issued an unprecedented warning to the cosmetics
industry stating that the Agency is serious about enforcing the law
requiring companies to inform consumers that personal care products
have not been safety tested.
http://www.rense.com/general7/whyy.htm
http://www.ewg.org/issues/cosmetics/FDA_Warning/
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NIH Guidelines: Recombinant DNA
molecules that are constructed outside living cells by joining natural or
synthetic DNA segments to DNA molecules that can replicate in a
living cell.
U.S. National Organic Standards Board definition of genetic
engineering & GMOs: "Made with techniques that alter the
molecular or cell biology of an organism by means that are not
possible under natural conditions or processes… It shall not include
traditional breeding, conjugation, fermentation, hybridization,
in-vitro fertilization, or tissue culture."
http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_02.htm#_Toc7261549
http://www.omri.org/OMRI_GMO_policy.html
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Conjugation
Rapid alternative to DNA transformation?
Conjugation between bacterial and
mammalian cells. Waters VL. Nat Genet.
2001
Transformation of isolated mammalian
mitochondria by bacterial conjugation.
Yoon YG, Koob MD. Nucleic Acids Res.
2005
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Organism Menu
Species
Generation
(hr)
Genome size
(Mbp)
Homologous
recombination
Library size,
comments
In vitro
.01 to 24
.0002
1
1E15
phage
.08
.008
1E-2
1E10
E.coli
.3
5
1E-4
1E9, tame
pathogen
S. cerevisiae
1.5
12
1E-3
1E7, tasty
Synechocystis
3
3.5
1E-3
?, green
C.elegans
48
100
RNAi
1E6, can of
worms
Mouse stem
cells
24
3000
1E-6 & RNAi
1E6,
cute
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.
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