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