Team:Nottingham/Model
Modelling
Aim: To model the interaction between bacteria and phage to gain insight into how we can best engineer and deliver phage to be an effective treatment against Chlostridium difficile infection.
The diagram above shows the two possible life cycles of phages. Following infection, phages following the lytic life cycle will hijack the host cell machinery to produce multiple copies of the phage proteins. These proteins are then assembled into multiple phage progeny which burst out of the host cell and go on to infect other bacterial cells. In the lysogenic life cycle, phages can integrate their genome into the host cell chromosome upon infection, where they can remain dormant for long periods of time as prophages. When conditions are favourable, usually due to host cell stress, prophage induction can occur. This is where prophages can excise from the host cell chromosome and enter the lytic life cycle leading to the production of progeny phage particles.
Click on the different sections to learn more about our modelling efforts and remember to refer back to the above diagram to help understand how our ODE models reflect the phage life cycles.
Summary
The main analytical result of our modelling work was the derivation of a condition that determines whether effective temperate phage therapy treatment can occur when prophage induction is allowed:
`\[\frac{(b-1)k_a}{d_P}>\frac{u}{c(u-q_0-d_X)}.\]`
Our estimated parameters satisfy this inequality so provided our antisense RNA and dCas9 contructs are effective at suppressing toxin production in lysogens this should lead to a stable population of non-toxigenic C. difficile and SBRC phage which would help to prevent reinfection. We also noticed with our induction model that initial phage dose is less crucial to effective treatment. This is particularly important since we gathered from Dr Cath Rees that high phage titre, are difficult to produce and would lead to a costly therapy. Therefore, the ability of our phage to be effective at a low initial dose should lead to a more affordable treatment. From these results we decided to allow SBRC phage to undergo prophage induction at its natural rate instead of preventing induction as we had initially planned.
