Contract : Fixed-term contract, PhD fellowship
Duration : 36 months
Funding is provided by the ANR.
Start date : 01/01/2022
Laboratory : Institute for Neurosciences of Montpellier
Oculocutaneous albinism (OCA) is the most common hereditary cause of generalized hypopigmentation, which results in severe visual deficits in patients. Molecular links between genetic defects, developmental pathways and clinical signs remain poorly understood, especially with regards to the pathophysiology of the ocular defects. As part of an ANR-funded national collaborative project (OCAGEN), we aim to unravel the molecular mechanisms impacting pigmented cells and ocular disease outcome by combining the state-of-the-art techniques of iPSC and CRISPR/Cas genome editing. The selected candidate will generate iPSC lines knocked-out for 5 different albinism genes and differentiate them into iPSC-derived retinal pigment epithelium and organoids. He/She will study these human retinal models at the morphological, functional and biochemical levels to elucidate the role of OCA genes in disease pathophysiology.
The applicant will join the “Gene therapy of inherited retinal dystrophies” group within the Vision team of the INM (http://www.inmfrance.com/inmfrance-j3/index.php/en/vision-en). This dynamic group is interested in developing innovative strategies to treat genetic retinal diseases
Mamaeva D, Jazouli Z, DiFrancesco ML, Erkilic N, Dubois G, Hilaire C, Meunier I, Boukhaddaoui H & Kalatzis V. (2021) Novel roles for voltage-gated T-type Ca2+ and ClC-2 channels in phagocytosis and angiogenic factor balance identified in human iPSC-derived RPE. FASEB J. 35:e21406.
Diakatou M, Dubois, G, Erkilic N, Sanjurjo-Soriano C, Meunier I & Kalatzis V. (2021) Allele-specific knockout by CRISPR/Cas to treat autosomal dominant retinitis pigmentosa caused by the G56R mutation in NR2E3. Int. J. Mol. Sci. 20: 2542.
Sanjurjo-Soriano C, Erkilic N, Baux D, Mamaeva D, Hamel CP, Meunier I, Roux AF & Kalatzis V. (2019) Genome Editing in Patient iPSCs Corrects the Most Prevalent USH2A Mutations and Reveals Intriguing Mutant mRNA Expression Profiles. Mol. Ther. Methods Clin. Dev. 17:156-173.
Torriano S, Erkilic N, Faugère V, Damodar K, Hamel CP, Roux A-F & Kalatzis V. (2017) Pathogenicity of a novel missense variant associated with choroideremia and its impact on gene replacement therapy. Hum. Mol. Genet. 26:3573-3584.
- Conduct cell culture experiments (iPSC culture, differentiation into retinal organoids)
- Conduct cell biology experiments (cryosections, immunofluorescence, immunoblot)
- Conduct molecular biology experiments (RNA/DNA extraction, qPCR, cloning techniques)
- Record and format results
- Communicate experimental data
- Control the disposal of solid waste and effluents according to the health and safety rules of the field
- General knowledge of cell culture and cellular and molecular biology
- Knowledge of health and safety rules related to work in confinement
- Knowledge of English: oral level B2, read and written level B2
- The candidate must be highly organized, rigorous and scientifically curious.
- He/She must be able to work as part of a team and possess strong communication skills.
- Experience in human cell culture experience would be an advantage.
- Work in a containment laboratory
- Occasional weekend work
- Master 2 in molecular biology