Difference between revisions of "Team:Nottingham/Lytic phage model"

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                <h2>Modelling</h2>
 
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                <h3>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 <em>Chlostridium difficile</em> infection.</h3>
 
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                <p>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
 
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                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
 
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                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
 
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                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
 
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                chromosome and enter the lytic life cycle leading to the production of progeny phage particles.</p>
 
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                <p>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
 
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                reflect the phage life cycles. </p>               
 
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<div class="item">Adapted a lytic model from literature to represent our initial plan for SBRC phage (no induction model).</div>
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<div class="item">Adapted model to include prophage induction</div>
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                                        <div class="item">Determined all equilibrium points of temperate phage models and relevant stability conditions.</div>
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                                        <div class="item">Estimated SBRC phage decay rate after noticing correlation between decay rate and burst size in a previous phage study.</div>
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                                        <div class="item">Determined other SBRC phage and <em>C. difficile</em> parameters from our experimental data and a literature search.</div>
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                                        <div class="item">Investigated and compared models analytically and numerically to determine which best suited our purpose.</div>
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                                        <div class="item">Proposed a model for the correlation between phage concentration and induction rate. Although this model is not influential for SBRC phage, it should be noted by other teams studying different phage.</div>
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<p>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:</p>
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<p>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 <em>C. difficile</em> 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.</p>
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<h2>Lytic phage model</h2>
 
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Revision as of 14:06, 17 October 2018

Clostridium dTox Project
Project description Abstract
Human Practices
Overview Silver Gold Safety and Ethics
Public Engagement
Discovery day School workshops Media
Lab
Ideas Design Results Conclusion Future Work Interlab Labfolder
Modelling
Introduction Summary Lytic Phage Models Temporate Phage Models Comparsion of all three models Methodology Parameters References
Collaborations
The University of Warwick Team BioMarvel- Korea The University of Warwick and Imperial College London UK Meetups
Achievements
Medal Criteria Parts Improved parts Demonstrate General conclusion
Team
Students Supervisors Principal Investigators
Attributions
Home
Lytic Phage Model

Lytic phage model

style

Temperate phage models

No induction model

Induction model

Induction as a function of P

Comparison of models

Methodology

Parameters

Achievements

References

Overview Summary Lytic phage model Temperate phage models Comparison of models Methodology Parameters Achievements References

About our sponsors
style