ABOUT ME
Micro-organisms, Evolution and consequences
My research is dedicated to explore virus evolution by experimental approaches with touch of modelisation.
How virus can overcome amiRNA resistance ? What is the dynamic of infection ? How and why measure evolution rate of gene in a same organism ? Is it advantagous to be specialized to a particular host ? Are question
Now I will present my work before my recruitment at the INRA, taking place in three laboratories recognized for their strong influence in science.
During one year, I was employed as assistant at Imperial College of London (U.K). I worked on the pathosystem Pseudomonas-Arabidopsis in the Murray Grant and Marta De Torres-Zabala’s laboratory. We studied the role of the abcissic acid hormone (ABA) on the strength of pathogenicity of Pseudomonas syringae. My role here was to determine the effect of ABA in different contexts for plants (wild-type or knock-out mutants) and bacteria (wild-type or non-pathogenic mutant) by bacterial population time course in plants, hormone and callose accumulation measurement. This work has been published in the Embo Journal (1).
My Phd work at the Prof Santiago F. Elena’s lab (Valencia, Spain) was focused on plant virus evolution. During the first part of my Phd, I studied the possibility of a virus (Turnip Mosaic Virus) to breakdown an artificial resistance mediated by artificial miRNA in transgenic plants. The strategy here was to generate population diversity by doing passages in different context (in wildtype or in presence of subinhibitory concentration of amiRNA). We have shown an ability to breakdown the resistance, enhanced when the virus evolve in presence of amiRNA. The results of this study are presented in two articles: one published in Journal of Virology (2) and the second in Molecular Biology of Evolution (3). Then we improved the amiRNA technology creating a polygenic resistance (by two amiRNA) (4).
I also developed a project on the relationship between virulence and fitness using a mutant collection of Tobacco Etch Virus (TEV). We encountered results that contradict to the classical theoretical assumption of trade-off between virulence and multiplication. These results were at the basis of an article in which we developed a model fitting our results (5).
In the second part of my Phd, I took part in an experimental evolution project studying the differences and generation of specialist/generalist populations. To do so, we generated 7 different histories (4 specialists and 3 generalists) and then compared them at the phenotypic level (infectivity and virulence) and at the sequence level (the entire genome was sequenced). We found a clear pattern of local adaptation of the virus to the host(s) they encountered during evolution but we did not detect any cost for generalists populations. At the sequence level we found shared mutations for different replicas in different histories sharing a same host during the experimental evolution. From this study, one article is published in MBE (6) and another to Evolution (7).
I worked also on the influence of primary source of infection on the dynamic disease. Results indicate a positive correlation between dosis of inoculum and time exposition of primary site of infection on the infection dynamic. We do not have evidence for interference between primary infection sites, indicating an independent action of each source of infection (8). We then extend the study of infection dynamic in plant for the intermediate between-cell level with two viruses (9)
Using a bioinformatic approach, I collaborated with Dr Bravo lab
(Barcelona, Spain) on two different viruses to propose a procedure for regrouping genes with similar evolutionary patterns in terms of phylogenetic relationships and evolutionary pressures in a same genome. This article is now published at BMC Evolutionary Biology (10).
After my Phd I joined the “Evolutive Epidemiology” group of Dr Sylvain Gandon (Montpellier, France). During this post-doc position I was interesting to evaluate the fitness of gram+ bacteria (Streptococcus thermophilus) using the CRISP-R system. The project here is to compete bacteria with different level of complexity of CRISP-R and study the influence on bacteriophage fitness. Results are published in Proceedings of the Royal Society B: Biological Sciences (11).
I then followed a full informatic formation allowed me to deal with different software. I am now more aware for programation, database construction and managment etc.
Bibliography:
(1) Marta de Torres-Zabala, William Truman, Mark H Bennett, Guillaume Lafforgue, John W Mansfield, Pedro Rodriguez Egea, Laszlo Bögre and Murray Grant. Pseudomonas syringae pv. tomato hijacks the Arabidopsis abscisic acid signalling pathway to cause disease. 2007. The Embo Journal.
(2) Guillaume Lafforgue, Fernando Martínez, Josep Sardanyés, Francisca de la Iglesia, Qi- Wen Niu, Shih-Shun Lin, Ricard Solé, Nam-Hai Chua, José-Antonio Daròs and Santiago F. Elena. Tempo and Mode of Plant RNA Virus Escape from RNAi-Mediated Resistance. 2011. Journal of Virology.
(3) Fernando Martínez, Guillaume Lafforgue, Marco J. Morelli, Nam-Hai Chua, José- Antonio Daròs, Santiago F. Elena. Populations Dynamics of Virus Escape Mutants in RNAi-mediated Resistant Plants at 1:5105 Resolution. 2011. Molecular Biology and Evolution.
(4) Guillaume Lafforgue, Fernando Martínez, Qi-Wen Niu, Nam-Hai Chua, José-Antonio Daròs and Santiago F. Elena. Improving the effectiveness of amiRNA- mediated resistance against Turnip mosaic virus by combining two amiRNAs or by targeting highly conserved viral genomic regions.
2013. Journal of Virology.
(5) Guillaume Lafforgue, Josep Sardanyés, Santiago F. Elena. Differences in Accumulation and Virulence Determine the Outcome of Competition during Tobacco etch virus Coinfection. 2011.PLoS One.
(6) Stéphanie Bedhomme, Guillaume Lafforgue and Santiago F. Elena. Multihost experimental evolution of a plant RNA virus reveals local adaptation and host specific mutations. 2012. Molecular Biology and Evolution.
(7) Stéphanie Bedhomme, Guillaume Lafforgue and Santiago F. Elena. Genotypic but not phenotypic historical contingency revealed by viral experimental evolution. 2013. BMC Evolutionary Biology.
(8) Guillaume Lafforgue, Nicolas Tromas, Santiago F. Elena and Mark Zwart. Dynamics of the establishment of systemic potyvirus infection: Independent yet sites cumulative action of primary infection.2012. Journal of Virology.
(9) Nicolas Tromas, Mark P. Zwart, Guillaume Lafforgue and Santiago F. Elena. Within- host spatiotemporal dynamics of plant virus infection at the cellular level. 2014. PLOS Genetics.