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Title : type I interferon and other pathological pathways connecting Mycobacterium tuberculosis and SARS-CoV-2 infection in the alveoli environment. 🫁 🔬
Context:
Airborne pathogen Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), one of the top leading causes of death worldwide due to a single infectious agent, with 11 million cases and ~1.3 million attributed deaths in 2022 (WHO report). Upon infection, Mtb reaches the alveolar space and comes in close contact with the alveolar epithelial cells and alveolar macrophages (MPs), its primary target cells. Betacoronaviruses constitute a viral family that encompasses SARS-CoV and MERS-CoV. Both are responsible for severe respiratory disease in humans and originated during epidemics in 2003 and 2012, respectively. With a latent TB reservoir just under a quarter of the word population, it was no surprise that in 2020, when the Covid19 pandemic caused by the new betacoronavirus SARS-CoV-2 emerged, led to multiple co-infections worldwide. Systematic reviews of the literature point to a worsening of respiratory symptoms in co-infected TB/COVID-19 individuals. Mtb and SARS-CoV-2 display different physiopathology, and learning about their interactions with the host may aid in the development of dedicated COVID-19-TB treatment strategies, and improve the medical management of tuberculosis patients infected with a betacoronavirus.
In this project, we will zoom on the type I interferon pathway, key in the physiopathology of both diseases, and open to other pathological pathways connecting the two pathogens.
We validated a model of Human PCLS to study the early steps of infection by Mtb and SARS-CoV-2. This enabled ex vivo infections in a preserved and functional lung micro-environment (Eymieux et al. 2024). The protocols were established to observe the intracellular pathogens infecting different cell types and to ascertain their impact on the subcellular architecture, using confocal imaging and transmission electron microscopy (TEM).
Objectives:
1) to elucidate the cellular targets of a productive and defective infection by Mycobacterium tuberculosis (Mtb) and SARS-Cov-2,
2) to identify the pathological pathways triggered by Mtb and SARS-Cov-2 infections in the alveoli (with a focus on type I interferon thanks to the collaboration with ICOA unit),
3) to understand the cross-talk between these two major pathogens.
Hosting laboratories:
The PhD student will spend time in two research units : UMR INRAE ISP at Nouzilly (Aude Remot, PhD, HDR, thesis director), and UMR INSERM MAVIVH in Tours (Sébastien Eymieux, MD, PhD, thesis co-supervisor). The laboratory of Pr Agrofoglio (Univ Orléans) is partner of this project and will provide chemical libraries of inhibitors to be tested during the PhD.
Profile and skills required:
Applicants should have a broad understanding of immunology and infectiology. She/he should be interested in working in a multidisciplinary and multicultural environment and should have good knowledge of English. Experiments with M.tuberculosis and SRAS-Cov-2 will be conducted in our BSL3 laboratory, which entry requires BCG vaccination.
>Scientific skills:
– Experience with standard immunology techniques (cell culture, flow cytometry)
– Good background in molecular biology techniques (RNA extraction, transcriptomic).
– Experience of Omic data analysis (R studio) will be appreciated.
– knowledge of microscopy imaging (confocal and/or TEM) would be a plus.
Qualities:
– Scientific rigor
– Good capacity to communicate and open-minded attitude
– Strong motivation and perseverance
Application:
_ Application until April 7th (strict deadline). CV, latest school marks, and cover letter emailed to [email protected] and [email protected]
_ Selection of 3 candidates by Aude Remot and Sébastien Eymieux for the 25th of April (candidates will be asked to register on ADUM)
_ Audition in front of the doctoral school jury 30/04/25 to select the PhD student
Full description of the PhD project :
https://lnkd.in/edFX5JDH
