LIFELINE: ex vivo Lung ventIlation and perFusion Experimental pLatform for PKPD studies of INhaled thErapeutics

Lead and collaborations: the scientific objective of the LIFELINE project is to develop the first ventilationperfusion ex vivo platform for the pharmacokinetic and pharmacodynamic (PK/PD) study of inhaled treatments. It will make possible to study the quantitative effects of different parameters on the absorption of inhaled drug in order to improve and personalize therapies and diagnostic contrast agents according to the different respiratory conditions. In order to achieve the success of this technological innovation, the work will be divided into 4 work packages (WP), which are described below (Figure 3): The objective of this doctoral thesis is to achieve the WP of the LIFELINE project with publication at different stages of the project (Figure 3). This 3-year position will be co-supervised by Pr Sophie Perinel Ragey, MD-PhD, intensivist and pulmonologist, who leads the research topic on ex vivo models in the laboratory and Pr Jérémie Pourchez, PhD, senior researcher at Ecole des Mines de Saint Etienne, expert in biomedical engineering and aerosol science (main publications available at https://www.emse.fr/~pourchez/) . In addition, this project will lead to local cooperation with the University Hospital of Saint Etienne and other teams working on the topic. The team has developed multiple collaboration with national and international teams to study aerosolized particles and models.

This doctoral position will be located in the thriving environment of the INSERM Unit U1059 (French national institute for health and medical research, https://sainbiose-lab.fr), supported by a large portfolio of academic and industry funding, at the School of Medicine campus in Saint Etienne (Jean Monnet university), and in direct proximity with the University Hospital and the Center for Biomedical and Healthcare Engineering of Ecole Nationale Supérieure des Mines de Saint-Etienne, one of the top 10 French graduate schools for science and technology. The team has over 10 years of international expertise in various ventilated ex vivo models (Figure 1), and has already developed a ventilated-perfused (V-P) ex vivo model for 2 years. The team is inherently multidisciplinary, and will bring the specific skills needed for each WP to ensure the success of the project. The successful candidate will be invited to author at least two publications and will have the opportunity to participate to national and international meetings. Thanks to this expertise in the field of ex vivo ventilation, the first prototype enabling ex vivo ventilation and perfusion of porcine lungs was designed and developed in our laboratory (Figure 2).  Indeed, the addition of perfusion to our previous model presents a major technological challenge as “fresh” respiratory tracts must be harvested and used immediately after the animal's death, imposing surgical restrictions, changes to supply chains and additional ethical constraints. After initial validation tests several technological challenges were overcome by adding mobilization, rewarming, modulation of specific negative pressure ventilation and recycling of perfusion fluids.

The successful candidate will work on a widely translational panel of experiments from respiratory physiology to ex vivo modeling, engineering, and finally pharmacokinetics. By the start of the position (~October 2025), the applicant must hold a Master 2 in biological or pharmaceutical sciences. Basic knowledge in aerosol science, anatomy and physiology will be appreciated. The candidate is expected to show curiosity for medical research and healthcare, be a team player, and willing to progress in English and French, whichever language(s) is(are) non-native. Equal consideration will be given to candidates regardless of gender, origin and nationality.