Team:TU-Eindhoven/Description

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Our project focuses on a relatively new form of {{:Team:TU-Eindhoven/Template:Tooltip | text=MRI | tooltip=Magnetic Resonance Imaging }}: {{:Team:TU-Eindhoven/Template:Tooltip | text=CEST | tooltip=Chemical Exchange Saturation Transfer }} imaging. CEST imaging proteins contain hydrogen atoms which can be used to create the same image quality as when conventional heavy metals are used. We use Escherichia coli to express CEST proteins that leads to CEST contrast when the bacteria sense a {{:Team:TU-Eindhoven/Template:Tooltip | text=hypoxic | tooltip=Low oxygen saturation }} environment, thus working as a production factory and delivery system for the CEST MRI contrast agent.  
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Our project focuses on a relatively new form of {{:Team:TU-Eindhoven/Template:Tooltip | text=MRI | tooltip=Magnetic Resonance Imaging }}: {{:Team:TU-Eindhoven/Template:Tooltip | text=CEST | tooltip=Chemical Exchange Saturation Transfer }} imaging. CEST imaging proteins contain hydrogen atoms which can be used to create the same image quality as when conventional heavy metals are used. We use ''Escherichia Coli'' as the [[Team:TU-Eindhoven/Chasis |'''CHASSIS''']] to express CEST proteins that lead to CEST contrast when the bacteria sense a {{:Team:TU-Eindhoven/Template:Tooltip | text=hypoxic | tooltip=Low oxygen saturation }} environment, thus working as a production factory and delivery system for the CEST MRI contrast agent.  
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We use ten proteins, all of which are rich in Lysine and Arginine content. These proteins were selected with the aid of the {{:Team:TU-Eindhoven/Template:Tooltip | text=Protein Data Bank | tooltip=PDB }}, a python program that analizes the obtained amino acid sequences and calculates the ratio of Lysine or Arginine to the total chain length, and molecular dynamics simulations which allowed us to revise the accessibility of the various exchangable hydrogen atoms of the Lysines and Arginines of the selected peptides.  
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We use ten [[Team:TU-Eindhoven/Production |'''PROTEINS''']], all of which are rich in Lysine and Arginine amino acids, which leads to a high CEST contrast. In order to achieve the production of the CEST MRI contrast agent by our bacteria, we must create a series of diverse [[Team:TU-Eindhoven/Modeling | '''MODELS''']] focusing on the different components of the MRI contrast agent production.  
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In order to achieve the production of our bacteria based CEST MRI contrast agent, we must create a series of diverse [[Team:TU-Eindhoven/Modeling | models]] focusing on the different components of the MRI contrast agent production. These models range from the selection of the most adequate proteins for CEST MRI to the behaviour of the FNR promotor and the bacterial killing mechanism.
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In the [[Team:TU-Eindhoven/Wetlab | '''LAB''']] we produced the CEST MRI proteins aerobically. To enable anaerobic expression, a specialized promoter was designed to react to change in oxygen saturation, thereby triggering the protein expression. After aerobic protein expression the proteins were tested for the quality of their contrast in an MRI machine.
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In the [[Team:TU-Eindhoven/Wetlab | lab]] we attempt to produce the CEST MRI proteins, both aerobically and anaerobically. To Enable the anaerobic expression specialized promotors are designed to react to the changes in oxygen saturation and ultimately trigger the protein expression. Once the protein expression is successful either aerobically or anaerobically, these proteins are tested for the quality of their contrast in an MRI machine.
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Based on the principle of our project, we propose two [[Team:TU-Eindhoven/Applications | '''APPLICATIONS''']], tumor CEST MR Imaging and tracking of bacteria in bacterial infections studies. After image acquisition our CEST protein production device can be deactivated and eliminated using the HSV Thymidine kinase/Ganciclovir system as a [[Team:TU-Eindhoven/KillingMechanism | '''KILLING MECHANISM''']].  
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Based on the principle of our project, we propose two [[Team:TU-Eindhoven/Applications | applications]], tumor CEST MR Imaging and tracking of bacteria in bacterial infections studies. It is well known that tumors present a hypoxic environment, therefore our bacteria can be injected into bloodstream to travel into the tumor region. Once in the tumor region, the hypoxic conditions of the area will trigger the production of the CEST proteins by the E. coli. generating the required CEST contrast agent for MRI. This will ensure that MRI contrast is created where tumors are present, and also provides a good means of tumor targeting for drug delivery systems in the future. Once the CEST MRI images have been taken, the bacteria will be killed and eliminated from the body using the Thymidine kinase/Ganciclovir system as a [[Team:TU-Eindhoven/KillingMechanism | killing mechanism]]. In order to be injected into the bloodstream the bacteria should be modified once more to avoid activating an immune response. Similarly, our production and delivery system can be used for tracking bacteria in bacterial infection studies.
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One of the most prominent threats to our project is the attitude of [[Team:TU-Eindhoven/Outreach|'''SOCIETY''']], which often has trouble coping with the idea of using live bacteria in living patients. Therefore, as our [[Team:TU-Eindhoven/Society|'''HUMAN PRACTICES PROJECT''']], we developed an online source of knowledge related to the explanation of common misconceptions within the field of synthetic biology. However, general safety, not only of our device, but also our own personal safety whilst participating is also important, and thus we take [[Team:TU-Eindhoven/Safety|'''SAFETY''']] issues into consideration in our project.
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Further steps include the modifications to the chasis of our device in order to avoid an immune system response, moreover it is necessary to include the kill switch in our device as safety lock.
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Latest revision as of 10:05, 26 October 2013

Project Description

TU-Eindhoven Images genDiagramI.png

Our project focuses on a relatively new form of MRI: CEST imaging. CEST imaging proteins contain hydrogen atoms which can be used to create the same image quality as when conventional heavy metals are used. We use Escherichia Coli as the CHASSIS to express CEST proteins that lead to CEST contrast when the bacteria sense a hypoxic environment, thus working as a production factory and delivery system for the CEST MRI contrast agent.

We use ten PROTEINS, all of which are rich in Lysine and Arginine amino acids, which leads to a high CEST contrast. In order to achieve the production of the CEST MRI contrast agent by our bacteria, we must create a series of diverse MODELS focusing on the different components of the MRI contrast agent production.

In the LAB we produced the CEST MRI proteins aerobically. To enable anaerobic expression, a specialized promoter was designed to react to change in oxygen saturation, thereby triggering the protein expression. After aerobic protein expression the proteins were tested for the quality of their contrast in an MRI machine.

Based on the principle of our project, we propose two APPLICATIONS, tumor CEST MR Imaging and tracking of bacteria in bacterial infections studies. After image acquisition our CEST protein production device can be deactivated and eliminated using the HSV Thymidine kinase/Ganciclovir system as a KILLING MECHANISM.

One of the most prominent threats to our project is the attitude of SOCIETY, which often has trouble coping with the idea of using live bacteria in living patients. Therefore, as our HUMAN PRACTICES PROJECT, we developed an online source of knowledge related to the explanation of common misconceptions within the field of synthetic biology. However, general safety, not only of our device, but also our own personal safety whilst participating is also important, and thus we take SAFETY issues into consideration in our project.