PhD Opportunity in Gene Therapy for Hearing & Balance Disorders – Apply Nowapplication
il y a 1 jour
Paris
🔬 PhD Position – Gene Therapy & Genome Editing for Sensory Disorders (Paris) Hearing, balance, and vision are essential for communication, mobility, and social integration, yet curative treatments remain unavailable for most inherited sensory disorders. Among these, Usher syndrome represents the leading cause of combined congenital deafness and progressive blindness, providing a unique and clinically relevant framework to develop gene-based therapeutic strategies across both the inner ear and the retina. Recent advances in adeno-associated viral (AAV) vectors and next-generation genome editing technologies have opened realistic prospects for curative interventions. However, major challenges still limit clinical translation, including efficient delivery into post-mitotic sensory cells, durability of therapeutic benefit, definition of therapeutic windows, and safety, particularly with respect to immune responses and off-target effects. This project aims to address these challenges by developing and validating scalable, human-compatible gene therapy strategies using clinically relevant models of Usher syndrome. It will leverage a unique set of humanized mouse models reproducing patient mutations, including newly developed conditional models with delayed sensory phenotypes, enabling investigation of therapeutic intervention before irreversible degeneration. Two complementary therapeutic approaches will be explored. First, dual-AAV gene supplementation will be used to restore expression of disease-causing genes that exceed standard vector capacity. This strategy has already demonstrated promising preliminary results, including preservation of vestibular function and delayed hearing loss in humanized models. Second, precision genome editing approaches, including base editing, will be developed to directly correct pathogenic mutations within their endogenous genomic context. This strategy offers a major advantage in terms of scalability, as it can be applied to a broad range of genes independently of coding sequence size. Therapeutic outcomes will be assessed through an integrated, multiscale phenotyping pipeline combining molecular, structural, functional, and behavioral analyses in both the inner ear and the retina. The inner ear will serve as a rapid and quantitative testbed to evaluate therapeutic efficacy, while retinal studies will provide validation in a clinically relevant context, particularly for progressive vision loss. Overall, the project will generate robust preclinical datasets defining efficacy, durability, safety, and therapeutic windows for gene supplementation and genome editing strategies. Beyond Usher syndrome, it will establish a transferable framework for the development of gene therapies targeting a wide range of inherited sensory disorders, with strong potential for clinical translation. 🎓 Candidate profile We are seeking an outstanding and highly motivated candidate aiming for a career in biomedical research. • MSc (or equivalent) in molecular/cellular biology, neuroscience, biotechnology, or related field, • Excellent academic record (top ranking comes first), • Strong background in molecular and/or cellular biology, with significant hands-on research experience (ideally including in vivo models or gene therapy), • Proven ability to conduct research with rigor, autonomy, and critical thinking, • Strong interest in translational research and innovative approaches (gene therapy, genome editing), • Ability to work in an interdisciplinary and collaborative environment, • Excellent English skills (written and oral) Application Email to & Applicants should submit: • CV (including grades and ranking if available), • Motivation letter, • Academic transcripts Selection will be based on academic excellence, motivation, and fit with the project. 🏛 Environment The project will be conducted at the Institut Pasteur (Institut de l’Audition) This provides a world-class, interdisciplinary environment combining gene therapy, neuroscience, and advanced imaging, with strong translational and clinical orientation. 🧬 Fields Biology (primary) | Neuroscience, Genetics, Molecular Biology, Gene Therapy, Translational Medicine