Inner ear organoids are self-organizing 3D tissue structures that can mimic the development of certain inner ear structures, including sensory cells and their associated neuronal cells. Since these organoids can be established from both mouse embryonic stem cells and human induced pluripotent stem cells, they have emerged as promising in vitro models for basic research in developmental biology, biomedical research and translational applications in the field of hearing. However, they currently lack the high spatial organization that is characteristic of the cochlea, the mammalian auditory organ.
The goal of this project is to generate inner ear organoids that can recapitulate in vitro the initial steps of the formation of the cochlear sensory epithelium. To this end, we propose to generate inner ear organoids in a microenvironment that implements the graded activity of some molecular factors called morphogens, known from mouse genetics studies to be critical for establishing the spatial organization of the auditory organ. We will combine microfluidics technology with high throughput imaging and stem cell biology, in order to study the conditions under which inner ear organoids become spatially patterned. This interdisciplinary project, which will involve the concerted effort of four teams from the Institut Pasteur of Paris, the Institut Pasteur of Korea and the University of Seoul, will represent the first step toward the generation of cochlear organoids.
Although the approach will be first developed on rapidly growing organoids from mouse embryonic stem cells, it will be directly applicable to human pluripotent stem cells with minor modifications to existing protocols. The culture system that we propose to implement should facilitate the study of human inner ear development and research on therapies for inner ear pathologies. Inner ear organoids are also a promising model in the context of regenerative studies of the mammalian auditory system, whose sensory cells have become specialized to the point of losing the ability to regenerate during evolution.
- Proficiency in stem cell biology and molecular biology.
- Strong interest in developmental biology.
- Good skills in imgaging (confocal microscopy) and image processing.
The project will be carried out on two different sites: 12 months in Institut Pasteur Paris (France) followed by 12 months in Institut Pasteur Seoul (Korea).