Download ALCOHOL vs. BRAIN - bli-research-synbio-2014-session-2

ALCOHOL vs. BRAIN
DRUNKENNESS PREVENTION
PURPOSE
Why is drunkenness prevention important?
Impaired memory and judgment
Drunk driving
accidents
Crime
What will my design do to address this
problem?
How does alcohol affect our brains?
Inhibit excitatory activity
Ethanol moleculeUncompetitive
antagonist
Synaptic plasticityLearning and memory
Glutamate
Ca2+
NMDAIonotropic glutamate
receptor
How is alcohol metabolized in the brain?
Acetyl-CoA
synthase-2
Acetyl-CoA
CO2
Water
Basic idea of my
design
• Prevent ethanol from blocking the
NMDA receptor for too long
• Alphaproteobacteria
• Quorum sensing
• Control alcohol concentration
• Produce enzymes invovled in alcohol metabolism
• Results: euphoria, but not too drunk
COMPETING TECHNOLOGIES
1. UCLA – dihydromyricetin (DHM)
•
•
•
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Ancient herbal remedy- Hovenia dulcis
Rats seem sober within 15 minutes
Dealing with hangover anxiety
Never become addicted- stop rats wanting to drink
2. Yale- iomanzenil
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Negate alcohol’s effect on the brain when taken before drinking
“stay sober” pill, slowly wean heavy drinkers off of alcohol
Problems?
•
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Take pleasure out of drinking
Encourage people to drink more, damaging body tissues
THE DESIGN
Quorum Sensing: Bacteria communication/ gene regulation
• Signal molecule: AHL
• Two genes: LuxI and LuxR
• Luxl:
– AHL synthase: combine AdoMet and fatty acyl ACP-> AHL
• LuxR:
– Transcriptional regulatory protein
– Activated when bind with AHL
Therefore, the more AHL is produced, the more chance that R protein
can bind to an AHL molecule. When a specific concentration threshold
is reached, the R protein is activated and so is the transcription.
Simple model of the Quorum Sensing process:
Genetic Devices:
1.
2.
3.
4.
5.
6.
Receptor protein that only bind to ethanol- Lush protein
Transcription factor activated by lush protein and controls the
transcription of LuxI and LuxR protein
A promoter site/ activator binding site
RNA polymerase
Terminator
Gene sequences
1.
2.
3.
4.
5.
LuxI
LuxR
CAT (catalase)
ALDH2 (aldehyde dehydrogenase)
ACSS1 (acetyl CoA synthase-2)
A complicated model of my design:
EXPECTED RESULTS
• Concentration threshold: 0.04%
• < 0.04% : nothing, enjoy the euphoria 
• > 0.04 % enzymes are produced for alcohol detoxification, keeping
alcohol concentration at 0.04%
ADVANTAGES
Why is this better than the existing technologies?
• allows you to still enjoy the pleasure of drinking
• no memory loss or impairment in judgment
• safer way to have fun
What benefits does it bring to the society?
• Less alcohol crimes (40%)
• Prevent alcoholism
POTENTIAL PROBLEMS
What are the potential problems with your system?
• No danger to environment, lab safety, or the security of the public
• Mutation
• Increased amount of alcohol consumption– harmful to other body parts
Are their inefficiencies or shortcomings of your design as
compared to the existing technologies?
• Permanent effect
• Involves complicated process to insert
the bacteria into the brain
Are the rewards worth the risks?
• Remove unnecessary genes
• Improve ethanol metabolism in other organs
• Less alcohol-induced tragedy and more fun!
TESTING
1. Rats
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•
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Control and experimental group
BAC 0.04%15 bottled beer
“heat shock” transformation
2. Human brain cells in vitro
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Bacteriophages
Add ethanol molecules till > 0.04%
3. Human in vivo
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Bacteriophages
Drink till 0.04%
Driving simulator
Drink till 0.08%
- THE END THANK YOU!