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Understanding host defense and parasite offense: the coevolution of circadian rhythms


School of Biological Sciences

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Prof S Reece , Dr N Savill No more applications being accepted

About the Project

Interested individuals should email [Email Address Removed] directly. Send a two page Curriculum Vitae including contact details for two academic referees; a one page statement of research interests and grades/transcript of marks.

The discovery of biological rhythms, such as circadian rhythms, in parasite behaviours [1] and host immune responses [2] suggests that timing matters for how hosts and parasites interact with each other. For example, the developmental rhythm of many malaria parasite species is coordinated; parasites invade host red blood cells, replicate, and then release their progeny in a timed, synchronized burst. However, to date, the study of parasite biological rhythms has rarely considered whether parasites are organising their own schedules or whether parasites are passive and scheduled by aspects of host physiology with circadian rhythms. Rhythms in immune defence and parasite development could provide an evolutionary advantage to hosts, parasites or both, and both parties may to some extent control each other’s rhythms [3]. This project will bridge this divide to investigate the evolutionary ecology of biological rhythms in host-parasite interactions.

The project will integrate the study of circadian rhythms, behavioural, and mathematical biology to investigate the evolutionary ecology of biological rhythms in host-parasite interactions. The project offers a novel opportunity to combine experiments and theory by collecting data from the lab [e.g. 1] and then using the data to undertake statistical inference of disease processes [e.g. 4, 5].

The project will focus on an established disease model (rodent malaria [1,4-7]) and specific topics that could form the focus of the PhD include:
(A) How are rhythms in parasite development initiated and maintained? Do parasites use their own time-keeping mechanisms to organise development or do they use cues from the host's circadian rhythms?
(B) How do rhythms affect the survival and transmission of parasites? Have parasites evolved time-keeping mechanisms to better exploit host resources or to evade immune killing?
(C) Are rhythms in parasite development and host immune responses adaptive for parasites, hosts, or neither?

We are looking for a highly motivated and exceptional candidate excited about working at the boundary of scientific disciplines. You should have, or expect to gain, a 1st or 2i degree classification in the life sciences. The project will be co-supervised by Sarah Reece and Nick Savill (Edinburgh) and is part of a larger project involving Nicole Mideo (Penn State/Toronto) and Bert Maier (Charite, Berlin) that is funded by a Human Frontiers of Science Project grant.

References

[1] O’Donnell A.J., Schneider P., McWatters H.G. & Reece S.E. (2011) Fitness costs of disrupting circadian rhythms in malaria parasites, Proceedings of the Royal Society of London, Series B, 278(171): 2429-2436



[2] Keller M., Mazuch J., Abraham U., Eom G.D., Herzog E.D., Volk H.D., Kramer A. & Maier B. (2009) 
A circadian clock in macrophages controls inflammatory immune responses.
Proceedings of the National Academy of Sciences, USA, 106(50):21407-12.



[3] Mideo, N., Reece, S.E., Smith, A. Metcalf, C.J.E. (2013) The Cinderella Syndrome: Why do malaria-infected cells burst at midnight? Trends in Parasitology, 29: 10-16.
[4] Miller M.R., Raberg L., Read A.F. & Savill N.J. (2010) Quantitative analysis of immune response and erythropoiesis during rodent malaria infection, PLoS Computational Biology, 6(9):e1000946.



[5] Mideo N., Savill N.J., Chadwick W., Schneider P., Read A.F., Day T. & Reece S.E. (2011) Causes of variation in malaria infection dynamics: insights from theory and data. American Naturalist, 178(6): E174-E188
[6] Pollitt L.C., Mideo N., Drew D., Schneider P., Colegrave N. & Reece S.E. (2011) Competition and the evolution of reproductive restraint in malaria parasites. American Naturalist, 177(3): 358-367

[7] Schneider P., Bell A.S., Sim D.G., O’Donnell A.J., Blanford A., Paaijmans K., Read A.F. & Reece S.E. (2012) Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi. Proceedings of the Royal Society of London, Series B 279(1747): 4677-85.



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