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Dr Oliver Restif

Research Interests

 

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), TJ McKinley and Julia Gog, 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
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? (in preparation)
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 have been setting up a new system in the lab, using the free-living nematode Caenorhabditis elegans as a host of various parasitic micro-organisms. Together with Dr Anaid Diaz, 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.
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
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

Restif O, Goh YS, Palayret M, Grant AJ, McKinley TJ, Clark MR, Mastroeni P. Quantification of the effects of antibodies on the extra- and intracellular dynamics of Salmonella enterica. J R Soc Interface. 2012 Dec 12;10(79):20120866.

 

Restif O, Hayman DT, Pulliam JR, Plowright RK, George DB, Luis AD, Cunningham AA, Bowen RA, Fooks AR, O'Shea TJ, Wood JL, Webb CT. Model-guided fieldwork: practical guidelines for multidisciplinary research on wildlife ecological and epidemiological dynamics. Ecol Lett. 2012 Oct;15(10):1083-94.

Gog JR, Murcia A, Osterman N, Restif O, McKinley TJ, Sheppard M, Achouri S, Wei B, Mastroeni P, Wood JL, Maskell DJ, Cicuta P, Bryant CE. Dynamics of Salmonella infection of macrophages at the single cell level.

J R Soc Interface. 2012 Oct 7;9(75):2696-707.

Goh YS, Grant AJ, Restif O, McKinley TJ, Armour KL, Clark MR, Mastroeni P. Human IgG isotypes and activating Fcγ receptors in the interaction of Salmonella enterica serovar Typhimurium with phagocytic cells. Immunology. 2011 May;133(1):74-83.

Restif O, Amos W. The evolution of sex-specific immune defences. Proc Biol Sci. 2010 Jul 22;277(1691):2247-55

Restif O, Grenfell BT. Vaccination and the dynamics of immune evasion. J R Soc Interface. 2007 Feb 22;4(12):143-53.