My research focuses on the evolution of pathogens to cross species-barriers and infect new hosts. In particular, using mathematical modelling of experimental data and next generation sequencing data, I am studying the potential of avian A/H5N1 influenza viruses to adapt to a human host. These highly pathogenic avian A/H5N1 (“bird flu”) viruses are a major public health concern, causing severe disease in infected humans, with over 50% mortality. When research groups reported that these viruses can become aerosol transmissible between mammals [Science 336: 1534–1541 (2012); Nature 486: 420–428 (2012)], we developed a mathematical model of within-host virus evolution that was used to provide an urgently needed detailed appraisal of the critical parameters involved in the host-adaptation process of A/H5N1 viruses [Science 336: 1541–1547 (2012)].
As a fellow, I am using computational data analysis and modelling techniques to improve the developed model of within-host virus evolution and help refine the estimate of the pandemic risk posed by influenza A/H5N1 viruses. In particular, I am using deep sequencing data to study the viral population diversity and dynamics, to investigate evolutionary mechanisms and biological parameters that our publication identified as important determinants in quantifying H5N1 pandemic risk. In addition to addressing fundamental and general scientific questions, this work ties in with the status of the Centre for Pathogen Evolution as a WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases, as it may inform policy decisions on the strategies for surveillance, mitigation, and global eradication of the virus.
I obtained my BSc (2005) and MSc (2007) degrees in Chemistry at the University of Nijmegen (The Netherlands), which included research projects in the Biophysical Chemistry department (Prof. S.S. Wijmenga), the Analytical Chemistry department (Prof. L.M.C. Buydens), and a 6-month period of research abroad in the department of Structural Biology at Stanford University (Prof. J.D. Puglisi), which was fully funded by a scholarship from the Huygens Scholarship Programme / Talent Programme. In 2006, I additionally attended 56th the Lindau Nobel Laurate Meeting for Chemistry.
I obtained my PhD degree in 2011 from Imperial College London, funded by a studentship from the Royal Society of Chemistry, on the “Development and application of chemometric methods for modelling metabolic spectral profiles” in the Department of Biomolecular Medicine (now Computational and Systems Medicine), with advisors Prof. J.K. Nicholson and Prof. E. Holmes. Examples of my research include the development of a method to acquire and process metabolic data in a manner that enhanced information retrieval and biomarker identification; the design of a toolbox to simplify the interpretation of mass spectrometry imaging data of tissue samples, as part of a large BRC-funded translational medicine project; and the development of open-source software for non-linear predictive modelling.
Upon finishing my PhD degree, I joined the Centre for Pathogen Evolution as a postdoctoral researcher, in which time I lead the modelling work on the within-host evolution of A/H5N1 influenza viruses, and I developed methodologies to analyse human serological data (antibody landscapes).
Currently, I hold an MRC Special Training Fellowship in Biomedical Informatics in the Centre for Pathogen Evolution in the Department of Zoology, and a Junior Research Fellowship at Homerton College.
Departments and Institutes
- Fonville JM*, Wilks SM*, James SL, Fox A, Ventresca M, Aban M, Xue L, Jones TC, Le NMH, Pham QT, Tran ND, Wong Y, Mosterin A, Katzelnick LC, Labonte D, Le TT, van der Net G, Skepner E, Russell CA, Kaplan TD, Rimmelzwaan GF, Masurel N, de Jong JC, Palache A, Beyer WEP, Le QM, Nguyen TH, Wertheim HFL, Hurt AC, Osterhaus ADME, Barr IG, Fouchier RAM, Horby PW, Smith DJ. Antibody landscapes after influenza virus infection or vaccination. Science 2014 (346): 996-1000. (* these authors contributed equally)
- Russel CA, Fonville JM, Brown AEX, Burke DF, Smith DL, James SL, Herfst S, van Boheemen S, Linster M, Schrauwen EJ, Katzelnick L, Mosterín A, Kuiken T, Maher E, Neumann G, Osterhaus ADME, Kawaoka Y, Fouchier RAM, Smith DJ. The potential for respiratory droplet–transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science 2012 (336): 1541–1547.
- Fonville JM¶. The expected effect of deleterious mutations on within-host adaptation of pathogens. Journal of Virology 2015 (89): 9242–9251. (¶ corresponding author)
- Fonville JM¶, Fraaij PLA, de Mutsert G, Wilks SH, van Beek R, Fouchier RAM, Rimmelzwaan GF. Antigenic maps of influenza A/H3N2 virus produced with human antisera obtained after primary infection. Journal of Infectious Diseases 2015: doi: 10.1093/infdis/jiv367.
- Fonville JM*, Marshall N*, Tao H, Steel J, Lowen AC. Influenza virus reassortment is enhanced by semi-infectious particles but can be suppressed by defective interfering particles. PLoS Pathogens 2015 (accepted).
- Fonville JM, Burke DF, Lewis NS, Katzelnick LC, Russell CA. Quantifying the fitness advantage of polymerase substitutions in influenza A/H7N9 viruses during adaptation to humans. PLoS ONE 2013 (8): e76047.