En combinant modélisation, outils Bayésiens et génomique des populations, Thierry Wirth caractérise les processus évolutifs et sélectifs qui sont responsables de la structuration des populations microbiennes, ainsi que de l’émergence de résistances aux antibiotiques. Ses travaux se déclinent sur plusieurs micro-organismes cibles (Escherichia coli, Helicobacter pylori, Staphylococcus aureus et Mycobacterium tuberculosis) et s’inscrivent dans le cadre de collaborations nationales et internationales.

Il a notamment contribué à révéler l’origine et la propagation de la peste à échelle planétaire par des approches NGS. Il est aussi à l’origine de travaux pionniers qui ont permis de démontrer un lien entre le sexe et la virulence chez Escherichia coli, proposant ainsi un nouveau paradigme du passage de souches avirulentes vers des souches pathogènes.

Actuellement, il se consacre à la reconstruction de l’histoire évolutive du bacille de Koch, qui demeure la principale source de mortalité (d'origine infectieuse) chez l’espèce humaine. A échelle macrogéographique, ses travaux permettent d’appréhender le rôle des migrations contemporaines dans la propagation de souches multirésistantes (MDR), alors qu’à échelle plus fine ils permettent des suivis épidémiologiques, ainsi que l’identification des sources potentielles d’épidémies en cours.

Depuis Septembre 2022, Thierry Wirth est détenteur d'une Chaire Leibniz au Leibniz Science Campus of Evolutionary Biology Medicine of the Lung (EvoLung) à Borstel, en Allemagne.

https://www.leibniz-gemeinschaft.de/en/ueber-uns/international/leibniz-chairs

Publications majeures:

1. Merker M, Rasigade JP, Barbier M, Cox H, Feuerriegel S, Kohl TA, Shitikov E, Klaos K, Gaudin C, Antoine R, Diel R, Borrell S, Gagneux S, Nikolayevskyy V, Andres S, Crudu V, Supply P, Niemann S, Wirth T (2022). Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis. Nature Communications, 15: 5105. IF = 17,70.

2. Wirth T (2021). When specialized clones go global. Nature Microbiology, 6: 1215-1216. IF = 30,96.

3. Wirth T, Bergot M, Rasigade JP, Pichon B, Barbier M, Martins-Simoes P, Jacob L, Pike R, Tissieres P, Picaud JC, Kearns A, Supply P, Butin M, Laurent F (2020). Niche specialization and spread of a Staphylococcus capitis clone involved in neonatal sepsis. Nature Microbiology, 5: 735-745. IF = 30,96.

4. Wirth T (2015). Massive lineage replacements and cryptic outbreaks of Salmonella Typhi in Eastern and South Africa. Nature Genetics, 47: 565-567. IF = 41,31.

5. Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, Blum M, Rüsch-Gerdes S, Mokrousov I, Aleksic E, Allix-Béguec C, Antierens A, Augustynowicz-Kopeć E, Ballif M,    Barletta F, Beck HP, Barry III CE, Bonnet M, Borroni E, Campos-Herrero I, Cirillo D, Cox H, Crowe S, Crudu V, Diel R, Drobniewski F, Fauville-Dufaux M, Gagneux S, Ghebremichael S, Hanekom M, Hoffner S, Jiao WW, Kalon S, Kohl TA, Kontsevaya I, Lillebæk T, Maeda S, Nikolayevskyy V, Rasmussen M, Rastogi N, Samper S, Sanchez-Padilla E, Savic B, Chola Shamputa I, Shen A, Sng LH, Stakenas P, Toit T, Varaine F, Vukovic D, Wahl C, Warren R, Supply P, Niemann S & Wirth T (2015). Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nature Genetics 47: 242-249. IF = 41,31.

PhD position on Mycobacterium tuberculosis adaptive landscape and epidemic success

Deadline for application: 2nd of June 11:59 pm
Audition : the 5th and 6th of June 2023

Job description:
We are looking for a talented and enthusiastic evolutionary, computational biologist for a fully funded 3-year PhD position, starting in September 2023. The successful applicant will work on a project aimed at understanding the epidemic success of multidrug-resistant tuberculosis lineages and their adaptive landscape. The PhD candidate will work in the research group of Prof. Dr. Thierry Wirth which is embedded within the ISYEB, at the Natural History Museum in Paris.
The work of Thierry Wirth's team focuses on an evolutionary lineage of the M. tuberculosis complex enriched in multidrug-resistant strains, the Beijing lineage, which is experiencing unprecedented success worldwide. In order to stem the spread of this pathogen, it is necessary to understand on the one hand what makes it successful and on the other hand, what are the selective forces and mechanisms at work. To this end, the thesis project will be divided into three parts. First, we will focus on the emergence and spread of multidrug-resistant strains in France. This part will be done in collaboration with the reference center of tuberculosis at the Pitié- Salpêtrière Hospital. We plan to sequence the complete genome of all MDR strains collected since 2006 on the French territory. A second step, more conceptual, will allow us to search by genome-wide associations (GWAS) for point mutations associated with the epidemic success of the Beijing lineage using a mathematical index developed within the team and which allows measuring the epidemicity of a strain. Finally, a third step aims at developing predictive simulations at the interface of results obtained in vivo in the laboratory in order to predict the speed of propagation of new variants (accumulating tolerance and antibiotic resistance mutations) within an individual or populations. The PhD candidate will receive varied and cutting-edge research training, with ample opportunities for following advanced courses, workshops and conferences, complemented by training in transferable skills and teaching. As a PhD candidate, you are committed to conduct independent and original scientific research, to report on this research in international publications and presentations, and to present the results of the research in a PhD dissertation, to be completed within 3 years.

Research scope and skills required:
The candidate should have broad interest in evolutionary biology and a strong background/experience in genomics, phyloepidemiology, GWAS, computational biology, forward simulations and scripting. Knowledge on M. tuberculosis epidemiology, metabolism and evolution is not mandatory but would be a bonus. She/he should also have good written and oral communication skills.
Applications:
Informal enquiries should be sent to Thierry Wirth (@email) before June 2nd, 2023. Formal applications should include (1) a cover letter detailing your research interests, experience and motivation for applying, (2) a CV, and (3) the names of two referees.