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Timetable (IDPW04)

Within-Host Modelling

Tuesday 7th July 2020 to Wednesday 8th July 2020

Tuesday 7th July 2020
14:00 to 16:00 Farzad Fatehi Chenar ; Raluca Eftimie ; Grant Lythe
Session 1

 


INI 2
14:05 to 14:30 Grant Lythe
Stochastic dynamics of Francisella Tularensis infection
Jonty Carruthers, Martin Lopez-Garcia, Grant Lythe, Carmen Molina-Paris (Leeds). Joseph Gillard, Thomas R Laws, Roman Lukaszewski
(Dstl)
With a mouse infection model, agent-based computation and mathematical analysis, we study the pathogenesis of Francisella Tularensis
infection. A small initial number of bacteria enter host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells.  Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously.  We compare our analysis with the results of agent-based computation and, via Approximate Bayesian Computation, with experimental measurements carried out after of murine aerosol infection with the virulent SCHU S4 strain of the bacterium.
If I have time, I will also talk about Ebola, still a significant risk to humankind. Synthetic virology has been used to clone and manufacture two deletion defective genomes. These genomes were tested with Ebola virus using in vitro cell culture and shown to inhibit viral replication.  From in vitro experimental data, we identify parameters in a mathematical model of the infection. We examine the time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity.


INI 2
14:30 to 15:00 Raluca Eftimie
Modelling virus infections in the context of cancer therapies (and other diseases)
Over the past years oncolytic viruses have generated much interest in cancer therapy, mainly due to the fact that once a virus is injected into the patient it can actively search for cancer cells and destroy them. However, the anti-tumour effect of oncolytic viruses is greatly diminished by anti-viral immune responses (both innate and adaptive responses), as well as by physical barriers inside the tumour. 
Using various single-scale and multi-scale mathematical modelling approaches, we will investigate the delicate balance between anti-viral and anti-tumour immune responses in the context of virus-tumour-immune interactions.





INI 2
15:00 to 15:30 Farzad Fatehi Chenar
Multiscale within-host modelling of SARS-CoV-2 infection reveals benefits and risks of early Remdesivir treatment
The SARS-CoV-2 outbreak has infected over ten million, and killed over 500,000, individuals worldwide, making the development of antiviral treatments against this virus a priority. Recent studies have identified Remdesivir as an effective antiviral treatment option for COVID-19. I will present a new stochastic agent based model for the intracellular dynamics of a SARS-CoV-2 infection that includes details on all essential steps of a viral life cycle, from viral entry to virion release. Using this model, I evaluate the effect of Remdesivir on the production of new virions. In a next step, I propose an intercellular model to study the viral dynamics within the body of an infected patient. The intercellular model is fitted to data recording the progress of viral load in 12 patients with COVID-19, showing how differing strengths of immune response can explain the variety of infection spans seen in patients. Coupling the intra- and intercellular models allows for a comparative analysis of Remdesivir therapy for patients with different types of immune response.




INI 2
15:30 to 16:00 Discussion INI 2
Wednesday 8th July 2020
12:00 to 13:00 Session 2 - PLENARY TALK by Ruth Bowness - University of St. Andrews - Modelling within-host tuberculosis infection using a hybrid multiscale individual-based model
INI 1
University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons