Our research is mainly divided into three main complementary areas
1. Bacterial propagation between cells
After invading the interior of its host cell, Shigella is known to hijack the actin cytoskeleton to generate physical forces that allow its intracellular motility and spread across the epithelium. Although it is commonly accepted that cell-to-cell dissemination is one of the critical steps for Shigella, but also for many other pathogens, the phenotype of this process seems to be heterogeneous today and the mechanisms favoring this dissemination are not fully understood. The MoHMI laboratory project aims to explore this behavior in a robust way in order to identify new determinants of Shigella tissue dissemination. To do so, we are developing a multi-scale phenotypic approach based on high-content imaging to obtain new information on host-microbe interactions at the micro (single cell) and macro (collective cell population) scales.
2. Role of mechanical forces in Shigella infection
Recently, our work has revealed that mechanical forces amplify the spread of Shigella through the epithelium. We now aim to determine at the molecular level how host cell physics influences Shigella infection. In particular, we are investigating how the mechanosensitive machinery of the host cell is involved in the formation and elongation of the inner membrane protrusions that allow Shigella bacteria to gain access to the neighboring cell.
3. Development of "Organ-on-a-chip" technologies
Like Shigella, many pathogens have a natural reservoir of infection restricted to humans. Therefore, the use of in vivo models such as small animals are often not fully satisfactory. Human in vitro models then play an important role in deciphering the molecular basis involved in Shigella infections. Recently, the development of microfluidics and bioengineering has increased the physiological relevance of in vitro systems by mimicking key aspects of human intestinal tissue, including 3D tissue microarchitecture. Pioneering the use of organs-on-a-chip for the study of enteroinvasive bacterial infections, our team is currently developing new "Organ-on-a-chip" methodologies to better understand the pathophysiology of epithelia.