Transcript Environmentally Controlled Invasion of Cancer

Environmentally Controlled Invasion of
Cancer Cells by Engineered Bacteria
Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
•Background
•Key Terms
Introduction
•Experiment
Results
Discussion
Background
•Since 1999, Cancer is the leading cause of
death in the U.S. for people under 85.
•There have been numerous approaches on
how to control and cure cancer.
•One way is to use proteins present in bacteria,
that allow interactions between bacteria and
cancer cells.
•They engineered bacteria to interact with
cancer cells depending on different
environments.
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
•Background
•Key Terms
Introduction
•Experiment
Results
Discussion
Background
•Using the invasin gene encoding invasin,
the quorum sensing lux operon and AHL
inducible lux promoter, the fdfH hypoxia
responsive promoter, and the arabniose
indubicle araBAD promoter, they engineered
bacteria to invade mammalian cells that
express beta-1 integrins.
•Their goal was to design a new approach to
engineer bacteria that would sense the
environment of a tumor and destroy them.
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
•Background
•Key Terms
Introduction
•Experiment
Results
Discussion
Key Terms
•Invasin is a long rigid protein that extends
about 18nm in length and binds tightly to
beta-1 integrins that are expressed by some
mammalian cells on their surface.
•The cancer cells they chose to invade were
HeLa HepG2, and U2OS lines.
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
•Background
•Key Terms
Introduction
•Experiment
Results
Discussion
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Experiment
Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
•Background
•Key Terms
Introduction
•Experiment
Results
Discussion
Experiment
•They constitutively expressed invasin under
the tet promoter (pAC-TetInv) in a mediumcopy plasmid.
•On a side note, the strain of E. coli they used
make type I pili (which bind to mammalian
surface carbs) encoded by the fim operon, so
their plasmid contains a deletion strain
(CAMC600).
•To determine how type I pili affected the
ability to invade, they also transformed
CAMC600 with pAC-TetInv
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
•Background
•Key Terms
Introduction
•Experiment
Results
Discussion
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Experiment
Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
Results
•fdfH + araBAD in
a BAC (Bacterial
Artificial
Choromose)
plasmid
•Lux, quorum
circuit with GFP
Results
fdfH + araBAD in a BAC (Bacterial Artificial
Choromose) plasmid
Discussion
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
Results
•fdfH + araBAD in
a BAC (Bacterial
Artificial
Choromose)
plasmid
•Lux, quorum
circuit with GFP
Results
Lux, quorum circuit with GFP
Discussion
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
Results
Discussion
Discussion
•Likes and Dislikes
Likes and Dislikes
I liked their new approach in serving cancer.
Demonstrated how one protein, invasin, can be used
in destroying tumor cells.
Created an inducible and constitutive system in
E. coli to attack the same cause. Allowed us to see
two different views in targeting tumor cells.
I disliked the invasin protein. Invasin binds to beta-1
integrins which are not on every cell, so if they were
to somehow create a treatment using invasin, it
would only work for some cancers.
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08
Introduction
Results
Discussion
Sources
Pictures from: Anderson JC, Clarke EJ, Arkin AP,
and Voigt CA. Environmentally controlled invasion of
cancer cells by engineered bacteria. J Mol Biol 2006
Jan 27; 355(4) 619-27.
Cancer cell photo from:
http://www.newscentre.bham.ac.uk/press/2007/10/C
ancer_Cold_Virus_03_10_07.shtml
That 1 cancer fact was taken from:
http://jnci.oxfordjournals.org/cgi/reprint/97/5/330.pdf
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Caltech iGEM Meeting #2 Presentation by Robert Ovadia
4/24/08