TEAM TU-EINDHOVEN
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TEAM TU-EINDHOVEN
MRI AND
BACTERIA AS
DIAGNOSTIC
TOOLS
THE ROAD TO OUR SOLUTION
TUMOR IMAGING
MRI scan of latter stages of brain cancer
Photograph by Zephyr/Science Photo Library
2007 National Geographic Society
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST)
ORGANIC CONTRAST AGENTS
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST)
ORGANIC CONTRAST AGENTS
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST)
ORGANIC CONTRAST AGENTS
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST)
ORGANIC CONTRAST AGENTS
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST)
ORGANIC CONTRAST AGENTS
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST)
ORGANIC CONTRAST AGENTS
THE ROAD TO OUR SOLUTION
BACTERIA BASED CANCER THERAPIES
Our Solution
TEAM TU-EINDHOVEN
Our Solution
TEAM TU-EINDHOVEN
Our Solution
TEAM TU-EINDHOVEN
Tumor Region
(Hypoxic
Environment)
TEAM TU-EINDHOVEN
Our Solution
TEAM TU-EINDHOVEN
The Sensor
The Chassis
Contrast
Agents
Safety
Detect the hypoxic environment
Generate contrast on an MRI scanner
Integrate the sensor and contrast agents
Ensure patient safety
The Sensor
TEAM TU-EINDHOVEN
Safety The Chassis Contrast
Agents The Sensor
TEAM TU-EINDHOVEN
The Sensor
Safety The Chassis Contrast
Agents The Sensor
Shift to low oxygen concentration
TEAM TU-EINDHOVEN
The Sensor
Safety The Chassis Contrast
Agents The Sensor
INTENSITY
INCREASES OVER
TIME
TEAM TU-EINDHOVEN
The Sensor
Safety The Chassis Contrast
Agents The Sensor
INTENSITY
INCREASES OVER
TIME
TEAM TU-EINDHOVEN
The Sensor
Safety The Chassis Contrast
Agents The Sensor
• High Lysine Ratio
TEAM TU-EINDHOVEN
Contrast Agents
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
1PJN
• Practicality
• Molecular
Dynamics
Simulations
TEAM TU-EINDHOVEN
// 1ETF
// 1G70
// 1PJN
// Human Protamine 1
// Poly Arginine-Glycine
// Poly Arginine-Serine
// Poly Threonine-Lysine
// Poly Lysine-Serine
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
THE SELECTION
Contrast Agents
AEROBIC EXPRESSION
NATIVE PROTEINS ARE CLEARLY EXPRESSED
TEAM TU-EINDHOVEN
Contrast Agents
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
TEAM TU-EINDHOVEN
Contrast Agents
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
TEAM TU-EINDHOVEN
Contrast Agents
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
THE BIOBRICKS
TEAM TU-EINDHOVEN
The Chassis
19 NEW BIOBRICKS:
- A FUNCTIONAL ANAEROBIC PROMOTER
(BBa_K1123000)
- 9 CEST PRODUCING PROTEINS
(BBa_K1123013 – BBa_K1123021)
- 9 COMPLETE TUMOR VISUALIZATION CONSTRUCTS
(BBa_K1123001 – BBa_K1123009)
Safety The Chassis The Sensor Contrast
Agents
The Safety Locks
TEAM TU-EINDHOVEN
Define
chassis Safety The Chassis The Sensor
Contrast
Agents
AVOIDING AN IMMUNE
SYSTEM RESPONSE
Outer
Membrane
Periplas
m
Cytoplas
mic
Membrane
Illustration by David S. Goodsell, the
Scripps Research Institute.
The Safety Locks
TEAM TU-EINDHOVEN
THE KILL SWITCH
Define
chassis Safety The Chassis The Sensor
Contrast
Agents
Herpes Simplex Virus Thymidine Kinase- Prodrug Ganciclovir System
TEAM TU-EINDHOVEN
THE KILL SWITCH MODEL
Define
chassis Safety The Chassis The Sensor
Contrast
Agents
The Safety Locks
BACTERIA AS
DIAGNOSTIC TOOLS: WILL SOCIETY ACCEPT
THE IDEA?
// Bringing the world of synthetic biology
into everybody’s home.
// Removing the reservations people
have about synthetic biology by
removing faulty data.
// Collaborating and collecting data
across the globe.
TEAM TU-EINDHOVEN
SYNTHETIC FACTS
Human Practices
TEAM TU-EINDHOVEN
SYNTHETIC FACTS
Human Practices
SYNTHETIC FACTS
21 Initial Facts To Be Checked.
12 Main Topics.
10 Facts Are Officially Checked, Uploaded And Available.
TEAM TU-EINDHOVEN
Human Practices
SYNTHETIC FACTS:
THE POLL
TEAM TU-EINDHOVEN
Human Practices
SyntheticFacts.tue.nl
FINAL
CONCLUSIONS
TEAM TU-EINDHOVEN
We have established
the foundations for a
new bacterial
application.
“Synthetic Facts” will
continue to give
reliable and unbiased
information.
TEAM PICTURE!!! Special Thanks To… // dr. Maarten Merkx
// dr. ir. Tom de Greef
// dr. ir. Natal van Riel
// ir. Stijn Aper
// Sagitta Peters MSc.
// Industrial Designer Mariana Felix
// ir. Stephanie Hectors
// prof.dr. Klaas Nicolaij
// dr. ir. Koen Pieterse
TEAM TU-EINDHOVEN
Acknowledgements
TEAM TU-EINDHOVEN
SUPPLEMENTAL
SLIDES
The Sensor
TEAM TU-EINDHOVEN
Global design of the FNR-single and FNR-tandem promoter
Reactions of the FNR-tandem
promoter
Safety The Chassis Contrast
Agents The Sensor
TEAM TU-EINDHOVEN
The Sensor
Safety The Chassis Contrast
Agents The Sensor
TEAM TU-EINDHOVEN
The Sensor
Safety The Chassis Contrast
Agents The Sensor
CEST PRINCIPLES
Contrast Agents
TEAM TU-EINDHOVEN
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
Tumor
Targeting
Kill Switch
Environmental
Sensor
Detectable by
CEST MRI
Escherichia Coli
The Chassis
TEAM TU-EINDHOVEN
Define
chassis Safety The Chassis
Contrast
Agents The Sensor
The Safety Locks
TEAM TU-EINDHOVEN
Define
chassis Safety The Chassis The Sensor
Contrast
Agents
AVOIDING AN IMMUNE
SYSTEM RESPONSE
Rough
Cytoplasm
Journal of Endotoxin Research, Vol.
7, No. 3 , 2001
Polysacchar
ide Surface
Layer
Outer
Membran
e
Cytoplasm
ic
Membrane
O-Antigen of LPS
K Capsule
Lipid A of
Lipopolysacch
aride (LPS)
Peripla
sm
Smooth
Rough
THE KILL SWITCH MODEL
TEAM TU-EINDHOVEN
Define
chassis Safety The Chassis The Sensor
Contrast
Agents
The Safety Locks
THE ALTERNATIVE
KILL SWITCH
TEAM TU-EINDHOVEN
The Safety Locks
Define
chassis Safety The Chassis The Sensor
Contrast
Agents
TEAM TU-EINDHOVEN
Modeling Overview
TEAM TU-EINDHOVEN
Modeling: Decoy Sites
TEAM TU-EINDHOVEN
Modeling: Integral Model
0 Decoy Sites
25 Decoy Sites
50 Decoy Sites
75 Decoy Sites
100 Decoy Sites
125 Decoy Sites
150 Decoy Sites
175 Decoy Sites
200 Decoy Sites
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