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Department of Veterinary Medicine

Cambridge Veterinary School

Studying at Cambridge

 

Dr Olivier Restif

Dr Olivier Restif

Alborada Lecturer in Epidemiology

Royal Society University Research Fellow

Director of Studies (NST Biology) for Robinson College

Olivier Restif is interested in taking PhD students.


Office Phone: +44 (0)1223 764963

Subject groups/Research projects

Infection and Immunity:
Mathematical Biology:

Research Interests

mouse

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 and Dybowski, 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. Our latest work revealed striking differences between vaccine types in their abilities to control the growth and spread of S. enterica in vivo. Our next project will investigate the effects of different antimicrobials. Together with Richard Dybowski, we are developing new inference methods to improve data analysis.

  • Key references: Coward et al (2014, PLoS Path), Mastroeni et al (2009, Nature Rev Microbiol), Grant et al (2008, PLoS Biol). 
  • Funding: BBSRC

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). 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? (Restif 2013)

*This particular paper stimulated an unusual amount of media coverage (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). We worked with Dave Lunn to develop a Bayesian framework that enabled us to fit complex mechanistic models to individual and population level data from these experiments (Lunn et al, 2013, PLoS One).

Since 2012, I have been working with Anaid Diaz on a new experimental system, using the free-living nematode Caenorhabditis elegans as a host of various bacterial pathogens. We 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. 

Funding: BBSRC

Collaborators: Hinrich Schulenburg 

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 supervised two PhD students: Wellcome Trust Fellow David Hayman and Gates Scholar Alexandra Kamins. With the support of the RAPIDD programme, we have been working with Colleen Webb's group to develop a a multi-disciplinary framework for model-guided field studies (Restif et al, 2012 Ecology Letters). In our latest study with Alison Peel, we used stochastic models to investigate the effects of seasonal birth pulses on the persistence of pathogens in wildlife populations (Peel et al 2013, Proc R Soc B).

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

Keywords

  • Bayesian Methods
  • Ecology
  • Mathematical modelling
  • Host-Pathogen Interaction
  • Evolution
  • Microbiology
  • Epidemiology
  • Infectious disease dynamics
  • Zoonoses
  • Salmonella enterica

Key Publications

  • Coward et al (2014) The Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivo. PLoS Pathogens, 10(9): e1004359, Full text 
  • Peel AJ et al (2014) The effect of seasonal birth pulses on pathogen persistence in wild mammal populations. Proc R Soc B, 281:20132962. Full text 
  • Restif O (2013) An offer you cannot refuse: down‐regulation of immunity in response to a pathogen's retaliation threat. J Evol Biol 26:2021-2030. Full text
  • Restif O et al. (2012) Model‐guided fieldwork: practical guidelines for multidisciplinary research on wildlife ecological and epidemiological dynamics. Ecology Letters 15:1083. Full text
  • Restif O & Amos W (2010) The evolution of sex-specific immune defences. Proceedings of the Royal Society B. Full text
  • 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, Grenfell BT (2007) Vaccination and the dynamics of immune evasion. Journal of the Royal Society Interface 4:143-153 [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]

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