Investigating a new effector function of therapeutic antibodies in the lungs

This thesis project explores a novel function of therapeutic antibodies (Abs), as immunomodulatory effectors inducing trained immunity (TI). Despite the availability of antibiotics, vaccines, and small molecule drugs, respiratory infection treatments remain inadequate, necessitating new approaches. This projet aims of understand the immunomodulatory functions of therapeutic Abs (through IC generation) on the innate immune system, potentially revealing a new role in immune memory and reprogramming. This novel concept of Abs inducing TI could enhance interest in Ab-based immunotherapies and help design new treatments against respiratory pathogens. Such treatments could not only neutralize pathogens but also provide long-term protection, combining the benefits of drugs and vaccines to significantly improve current strategies. The synergistic action of an anti-infective drug and vaccine in a unique Ab molecule to treat respiratory diseases has never been investigated or trialed and represents an innovative treatment approach.

Research hypothesis: We hypothesized that ICs may train innate immune cells to potentiate immune response after heterologous restimulation with pathogen associated molecular pattern (PAMPs).

To test this, we aim to:
-        Aim 1: Demonstrate the ability of therapeutic Abs to induce TI

-        Aim 2: Identify the molecular mechanisms triggering TI 
 

The Research Center for Respiratory Diseases (CEPR) is an academic laboratory comprising 4 teams situated in Tours , France, within the shared campus of the Faculty of Medicine and the Bretonneau University Hospital (CHU).
It was established in 2012 by the INSERM (National Institute of Health and Medical Research) and the University of Tours. Since then, CEPR is directed by Dr. Mustapha Si-Tahar (Inserm Research Director (DR1) ). Since 2024, he has also been supported by Dr. Fabrice Gouilleux (CNRS Research Director (DR2)) as Deputy-Director.

Our team, leaded by Dr. NAthalie Heuzé-Vourc'h, is focusing on inhaled biotherapeutics. Our main reseach areas are: 

- Studying the pharmacokinetics and pharmacodynamics of inhaled pharmaceuticals

- Developping inhaled formulations to improve drug stability/ efficacy

- Characterizing devices, drugs & devices for inhalation delivery

- Establising novel experimental models/ methods for inhalation to help translation into the clinics

Le candidat/e doit être titulaire d'un Master 2 dans le domaine de la biologie et avoir:

- une connaissance des fondamentaux en immunoligie

- des connaisances et compétences expérimentales en biologie moléculaires et cellulaires (expérience en expérimentation animale est un plus)

- un interet pour les biomedicaments

- un niveau de comprehension et expression en anglais correct

- des connaissances basiques en informatique (Rstudio et Phyton sont un plus)

Par ailleurs, il/elle doit être motivée et enthusiaste dans son travail.