Team:TU-Eindhoven/Modeling

The main objective of the modeling component of our project is to provide insight to the rest of team in what concerns the effect of altering the necessary conditions for the proper operation of each component of our device. Keeping this in mind we established a series of questions that if answered thoroughly would benefit our project. We categorized these questions in four main topics:

Protein Selection

1. Which proteins that can be expressed in bacteria are best suited as CEST based markers?

Gene expression

1. How does the oxygen concentration affect the concentration of the transcription activator (FNR) in its active form?
2. How does introducing decoy sites influence the gene expression rate?

CEST MRI Contrast agent

1. What is the average protein concentration produced by the bacteria?
2. What the estimated CEST contrast given by the bacteria?

Tumor Imaging In Vivo

1. How do bacteria distribute within the human body?
2. How long does it take for the bacteria to reach the target area?
3. How do the bacteria react to the activation of the killing mechanism?
4. What is the bacteria elimination rate?

Based on the previous question list we developed five models that can be divided into two categories, processes occurring inside the bacteria and the interaction of the bacteria with its surroundings. presents a schematic diagram of the developed models related to the first category, while depicts the model that accounts for the interaction between the bacteria and its surroundings when introduced into the human body for tumor imaging. Both figures will be further explained in the next paragraphs. The approaches used for the models range from molecular dynamics simulations to deterministic models and stochastic simulations as well as pharmacokinetics.

eColiModelsFigure General Models of Processes Happening Inside the E. Coli.

As previously mentioned, aims to schematically depict all the models that are related to the diverse components of our device, e.g the proteins that will be produced by the device, the FNR promotor and decoy sites which are related to the gene expression, and the CEST protein production directly related to the CEST MRI contrast agent.

PBPKFigure Model That Depicts The Administration Of The CEST MRI Contrast Producing Bacteria Into The Patient's Bloodstream.