A dynamical systems approach to determine the role of resistance and tolerance to surviving infections
Dr A Wilson
Prof A Lengeling
No more applications being accepted
Funded PhD Project (Students Worldwide)
Supervisors: Dr Andrea Doeschl-Wilson, Dr Nikola Popovic and Dr Andreas Lengeling
Why do some species or individuals die when infected with pathogens whereas others experience hardly any harm? Why is Ebola lethal for many humans whereas bats are naturally immune to the virus?
There are two alternative mechanisms that individuals can adopt to cope with infections: (i) restrict the reproduction rate of infectious pathogens within the host (called resistance) and (ii) minimise the damage that pathogens can inflict on the host (called tolerance). Our recent study of infection trajectories of genetically diverse mice suggests that survival depends on a fined tuned balance between both mechanisms, and that a different mechanism is prioritised at different stages of infection (Lough et al., Proc R. Soc. 2015). Knowing which mechanism dominates the host response to infection at different stages of infection, and which combination leads to recovery from the infection, is crucial for developing effective treatment.
In this project we will develop a generic dynamic mathematical model of the inflammatory response to infection that captures the interaction of resistance and tolerance immune mechanisms and their effect on health over time. We will use this model and harness the toolbox of mathematical dynamical systems theory to explore infection trajectories and determinants of survival.
The model will be informed by unique datasets consisting of detailed immune and health measurements from diverse infection experiments on mice (bacteria, Ebola and MERS virus) that have been collected in previous and current projects.
This 3 year PhD is a joint project between the Roslin Institute and the Department of Mathematics of the University of Edinburgh.
The successful candidate should have, or expect to have an Honours Degree at 2.1 or above (or equivalent) in Pure or Applied Mathematics, Physics, Theoretical Biology, or Computing Sciences. Preference will be given for students who have also expertise in one or more of the following topics: dynamical systems theory, mathematical modelling and statistical analysis of biological systems.
For further enquiry please email Dr. Andrea Doeschl-Wilson ([Email Address Removed]) or Dr. Nikola Popovic ([Email Address Removed]).
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to [Email Address Removed].
When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.
All applicants should also apply through the University’s on-line application system for September 2016 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=830
International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).
ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 1st FEBRUARY 2016
Rasmussen, Angela L., et al. "Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance." Science 346.6212 (2014): 987-991.
Lough, Graham, et al. "Health trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome." Proc. R. Soc. B. Vol. 282. No. 1819. The Royal Society, 2015.
Reynolds, Angela, et al. "A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation." Journal of theoretical biology 242.1 (2006): 220-236.