Department of Veterinary Medicine

Research in Veterinary Medicine

Other related links

• Royal Society
• Robinson College

Research description

I use mathematical models combined with experimental and field-based studies to investigate the dynamics of infectious diseases at all scales, from cells to ecosystems. My research falls into four main subjects:

A. Within-host dynamics of bacterial infections.
In collaboration with the Bacterial Infections Group, Mastroeni, Bryant, Maskell, Grant, Gog, McKinley we have been developing an integrated, multi-disciplinary framework to quantify the dynamics of acute and systemic Salmonella enterica infection, since 2004. Innovative experimental techniques (in situ multi-colour fluorescence microscopy, confocal microscopy, quantitative PCR and genetic engineering, with both in vitro macrophage cultures and in vivo infections of mice), combined with sophisticated modelling techniques (branching processes, stochastic simulations, likelihood and Bayesian statistics) have enabled us to quantify the interactions between bacteria and the host's immune system with unrivalled resolution.

• Key reference: Mastroeni, Grant, Restif & Maskell (2009, Nature Reviews Microbiology) doi:10.1038/nrmicro2034

• Funding: BBSRC

• Job opportunity: A 24-month post-doctoral position will be available in the Spring of 2012 to develop mathematical and statistical models as part of this project.

B. Evolutionary ecology of immune defences.
This is a theoretical thread of research I have been investigating since 2000 (initially with my PhD supervisor Jacob Koella [Jacob Koella). I use adaptive dynamics (derived from game theory) to try and understand how ecological dynamics affect the selective pressures on immune defences in the presence of a pathogen. While this work is not related to any specific empirical system, it aims to address questions of general interest in evolutionary biology that could impact our understanding of host-pathogen interactions (references below): - How do multiple defence strategies interact? (Restif et al 2001, Restif & Koella 2004) - How does pathogen coevolution affect selection on defences? (Restif & Koella 2003) - Should males and females invest equally in immune defences? (Restif & Amos 2010)* - Can plasticity in virulence expression force a host to delay the onset of its adaptive immune response? (in preparation)

*This particular paper stimulated an unusual amount of media coverage which would make an interesting case study on science reporting in the news (http://www.google.co.uk/search?q=restif%20man%20flu).

C. Microcosm studies of host-pathogen population dynamics.
My first incursion in experimental ecology took place during my PhD thesis in Paris, under the supervision of Oliver Kaltz when we set up a new lab-based model consisting of the Ciliate protozoan Paramecium caudatum and its bacterial parasite Holospora undulata (Restif & Kaltz 2006). Starting in 2011 I am setting up a new system in the lab, using the free-living nematode Caenorhabditis elegans as a host of various parasitic micro-organisms. I will combine experimental and theoretical work to quantify the dynamics of infection at the levels of individual hosts and populations, paving the way for an integrative model to study the evolution of host-pathogen interactions. I am also working with Dave Lunn to develop a Bayesian framework that enables us to fit complex mechanistic models to inidividual and population level data from microcosm experiments.

Funding: BBSRC

Collaborators: Hinrich Schulenburg, Jonathan Hodgkin, Robin May

D. Model-Guided Fieldwork for Wildlife Infectious Diseases.
I have been collaborating with James Wood, Andrew Cunningham and Tony Fooks on a research programme on the ecology and epidemiology of zoonotic viruses in the African Straw-Coloured Fruit Bat (Eidolon helvum). In addition to advising on study design, I have been supervising two PhD students: Wellcome Trust Fellow David Hayman and Gates Scholar Alexandra Kamins With the support of the RAPIDD programme, we are working with Colleen Webb's group to develop a a multi-disciplinary framework for model-guided field studies.

Funding: CIDC, ZSL, AHVLA, Wellcome Trust, Gates Cambridge Trust, RAPIDD, RCUK.

Key publications since 2001

• Restif O & Amos W (2010) The evolution of sex-specific immune defences. Preceedings of the Royal Society B published online
• Restif O (2009) Evolutionary epidemiology 20 years on: Challenges and prospects. Infection, Genetics and Evolution 9 (1): 108-23. [PubMed]
• Grant AJ, Restif O, McKinley TJ, Sheppard M, Maskell DJ, Mastroeni P (2008) Modelling within-host spatiotemporal dynamics of invasive bacterial disease. PLoS Biology 6:e74 [PubMed]
• Restif O, Wolfe DN, Goebel EM, Bjørnstad ON, Harvill ET (2008) Of mice and men: asymmetric interactions between Bordetella pathogen species. Parasitology 135: 1517-1529. [PubMed]
• Restif O, Grenfell BT (2007) Vaccination and the dynamics of immune evasion. Journal of the Royal Society Interface 4:143-153 [PubMed]
• Wolfe DN, Goebel EM, Bjørnstad ON, Restif O, Harvill ET (2007) The O antigen enables Bordetella parapertussis to avoid Bordetella pertussis-induced immunity. Infection and Immunity 75:4972-4979 [PubMed]
• Restif O, Grenfell BT (2006) Integrating life history and cross-immunity into the evolutionary dynamics of pathogens. Proceedings of the Royal Society of London, series B 273:409-416 [PubMed]
• Restif O, Kaltz O (2006) Condition-dependent virulence in a horizontally and vertically transmitted bacterial parasite. Oikos 114:148-158
• Restif O, Koella JC (2004) Concurrent evolution of resistance and tolerance to pathogens. The American Naturalist 164:E90-E102 [PubMed]
• Restif O, Koella JC (2003) Shared control of epidemiological traits in a coevolutionary model of host-parasite interactions. The American Naturalist 161:827-836 [PubMed]
• Koella JC, Restif O (2001) Coevolution of parasite virulence and host life history. Ecology Letters 4:207-214
• Restif O, Hochberg ME, Koella JC (2001) Virulence and age at reproduction: new insights into host-parasite coevolution. Journal of Evolutionary Biology 14:967-979