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Dr Judith M Fonville

Research Interests

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 virusesIn 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.

Keywords

data visualisation ; avian ; evolution ; antibodies ; medical informatics ; vaccines ; antibody responses ; bioinformatics ; systems biology ; metabolomics ; viral immune evasion ; immune response ; RNA viruses ; mathematical modelling

Topics

  • influenza
  • immunology
  • vaccines
  • dengue fever
  • infectious diseases

Key Publications

  • 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.

Other Publications

  • Katzelnick LC, Fonville JM, Gromowski GD, Arriaga JB, Green A, James SL, Lau L, Montoya M, Wang C, VanBlargan LA, Russell CA, Thu HM, Pierson TC, Buchy P, Aaskov JG, Muñoz-Jordán JL, Vasilakis N, Gibbons RV, Tesh RB, Osterhaus ADME, Fouchier RAM, Durbin A, Simmons CP, Holmes EC, Harris E, Whitehead SS, Smith DJ. Dengue viruses cluster antigenically but not as discrete serotypes. Science 2015 (349): 1338–1343.
  • Huang S.-W., Tai C.-H., Fonville JM, Lin C.-H., Wang S.-M., Liu C.-C., Su I.-J., Smith DJ, Wang J.-R. Mapping enterovirus A71 antigenic determinants from viral evolution.  Journal of Virology 2015 (accepted).
  • Fonville JM, Carter CL, Pizarro L, Steven RT, Palmer AD, Griffiths RL, Lalor PF, Lindon JC, Nicholson JK, Holmes E, Bunch J. Hyperspectral visualization of mass spectrometry imaging data. Analytical Chemistry 2013 (85): 1415–1423.
  • Fonville JM, Carter CL, Cloarec O, Nicholson JK, Lindon JC, Bunch J, Holmes, E. Robust data processing and normalization strategy for MALDI mass spectrometric imaging. Analytical Chemistry 2012 (84): 1310–1319.
  • Fonville JM, Swart M, Vokáčová Z, Sychrovský V, Šponer JE, Šponer J, Hilbers CW, Bickelhaupt FM, Wijmenga SS. Chemical shifts in nucleic acids studied with density functional theory calculations and comparison with experiment. Chemistry – a European Journal 2012 (18): 12372–12387.
  • Maher AD, Fonville JM, Coen M, Lindon JC, Rae CD, Nicholson JK. Statistical total correlation spectroscopy scaling for enhancement of metabolic information recovery in biological NMR spectra. Analytical Chemistry 2012 (84): 1083–1091.
  • Ferguson LS, Wulfert F, Wolstenholme R, Fonville JM, Clench MR, Carolan VA, Francese S. Direct detection of peptides and small proteins in fingermarks and determination of sex by MALDI  mass spectrometry profiling. Analyst 2012 (137): 4686–4692.
  • Fonville JM, Bylesjö M, Coen M, Nicholson JK, Holmes E, Lindon JC, Rantalainen M. Non-linear modelling of 1H metabonomic data using kernel-based OPLS optimized by simulated annealing. Analytica Chimica Acta 2011 (705): 72–80.
  • Fonville JM, Maher AD, Coen M, Holmes E, Lindon JC, Nicholson JK. Evaluation of full-resolution J-resolved 1H NMR projections of biofluids for metabonomics information retrieval and biomarker identification. Analytical Chemistry 2010 (82): 1811–1821.
  • Fonville JM, Richards SE, Barton RH, Boulange CL, Ebbels TMD, Nicholson JK, Holmes E, Dumas ME. The evolution of partial least squares models and related chemometric approaches in metabonomics and metabolic phenotyping. Journal of Chemometrics 2010 (24): 636–649.
  • Richards SE, Dumas ME, Fonville JM, Ebbels TMD, Holmes E, Nicholson JK. Intra- and inter-omic fusion of data in metabolic profiling. Chemometrics and Intelligent Laboratory Systems 2010 (104): 121–131.
  • Saric J, Li JV, Utzinger J, Wang Y, Keiser J, Dirnhofer S, Beckonert O, Sharabiani MTA, Fonville JM, Calvert G, Nicholson JK, Holmes E. Systems parasitology: Effects of fasciola hepatica on the neurochemical profile in the rat brain. Molecular Systems Biology 2010 (3): 396.