Team:ETH Zurich/Model/In Vivo

• Project Idea
  • Story of CATE
  • CATE in Action
  • Circuit
  • Design
• Engineering
  • Dry Lab
  • Overview
  • Tumor Sensor
  • Heat Sensor
  • 3D Model
  • Final Integration

  • Wet Lab
  • Experiments
  • Lab Journal
  • Protocols
  • Safety
  • Sequences
• Achievements
  • Results
  • Parts
  • Medal Criteria
  • InterLab
  • Collaborations
• Human Practices
  • Overview
  • Integrated Practices
  • Public Engagement
• Our Team
  • Attributions
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Behavior of CATE inside Tumor

We developed a model to gauge the behavior of our sensing circuit in the real life conditions of solid tumor colonization. Since it was not practically feasible to conduct experiments of bacterial colonization inside tumors, we used literature data from reference to simulate different bacterial colonization patterns.

The following were simulated using COMSOL:

• Diffusion physics added to extend the ODEs used earlier into PDEs
  
  • AHL diffusion as it is produced
    

  • Temperature controlled trigger of Azurin diffusion to simulate effect of lysis
    

  The ODEs as formulated in linkToPage were extended to include diffusion in case of AHL and Azurin. Diffusion coefficients and other parameters are given in linkToParameterSpace. To simulate effect of lysis, Azurin production is stopped and Azurin diffusion is started using a trigger controlled by a Temperature step function which simulates the increase in the local temperature due to FUS. Protein E dynamics have not been used for the lysis, as they were not necessary.

• Different bacterial colonization patterns
  
  • Homogeneous distribution in a Single spherical shell layer in tumour
    

  • Heterogeneous distribution in a Single spherical shell layer in tumour
    

  • Heterogeneous distribution in Double spherical shell layer in tumour
    

  • Homogeneous distribution throughout Healthy tissue
    

  As explained in linkToModelPage bacteria are shown to colonize in a spherical shell layer. We also tried a few other colonization patterns to show our system works as expected in a tumour while stays dormant in healthy tissue.

Model Overview

MAGIC!

• Parameters

• Equations
  • Growth phase
    

  • Sensing (AHL and LuxI)
    

  • Azurin
    

• Assumptions

Results

Beautiful GIFs coming soon .... MUST REALLY SOON

• CASE: Tumour colonization - High d_cell AND High Lactate

• CASE: Healthy tissue colonization: High d_cell AND Low Lactate

  

  

• CASE: Tumour not colonized: Low d_cell AND High Lactate

• CASE: Healthy tissue not colonized: Low d_cell AND Low Lactate

Bacterial colonization patterns

Beautiful GIFs coming soon .... MUST REALLY SOON

• Homogeneous distribution in a Single spherical shell layer in tumour

• Homogeneous distribution throughout Healthy tissue

• Heterogeneous (Partitioned) distribution in a Single spherical shell layer in tumour

• Heterogeneous (Partitioned) distribution in Double spherical shell layer in tumour

Tool used

COMSOL 5.2a, 5.3 and MatLab R2016b

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