Postdoctoral Researcher - Genome Editing for Genetic Skin Diseases (F/M)

About us Premier pôle européen de recherche, de soins et d'enseignement sur les maladies génétiques créé en 2007 au cœur du campus de l'Hôpital Necker-Enfants malades. Sa mission ? Mieux comprendre les maladies génétiques pour mieux les guérir. L'Institut Imagine est un endroit unique au monde qui rassemble chercheurs, patients, médecins et personnels de santé dans une architecture créatrice de synergies au service d'une même ambition : changer la vie des familles touchées par les maladies génétiques. Mission About the position The laboratory “Genetic Skin Diseases: from Pathophysiological Mechanisms to Treatments”, led by Prof. Alain Hovnanian at the Imagine Institute (INSERM UMR 1163), is seeking a highly motivated Postdoctoral Researcher to develop innovative genome editing strategies for genetic skin diseases. The position will be based in the Gene Editing subgroup under the supervision of Dr. Araksya Izmiryan. The postdoctoral researcher will contribute to an ANR-funded research project focused on the development of therapeutic genome editing approaches for epidermolysis bullosa. The project combines base editing and prime editing with patient-derived primary, induced pluripotent stem cells (iPSCs), and advanced skin organoid models to investigate and validate mutation-specific correction strategies. Research project The project aims to develop and evaluate precise genome editing approaches in clinically relevant human cellular and tissue models. A particular focus will be placed on editing patient-derived cells, followed by functional validation in 3D skin models and skin organoids. The project also incorporates single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to provide high-resolution molecular and spatial characterization of patient-derived skin organoids and edited skin models. Main responsibilities • Design, implement and optimize base editing and prime editing strategies;

• Design and characterize guide RNAs, including assessment of editing efficiency, specificity and potential toxicity;
• Develop and evaluate delivery strategies, including lipid nanoparticles (LNPs);
• Perform genome editing in human keratinocytes, fibroblasts and patient-derived RDEB iPSCs;
• Culture and maintain human iPSCs and and contribute to their differentiation into relevant skin cell populations;
• Develop, culture and characterize patient-derived skin organoids and 3D skin equivalents for disease modelling and functional validation;
• Perform molecular and cellular biology analyses, including DNA/RNA/protein extraction, PCR, RT-PCR, Sanger and NGS sequencing, FACS, immunocytochemistry and immunohistochemistry;
• Assess correction at the molecular and functional levels, including dermal–epidermal junction integrity and collagen VII expression in relevant epidermolysis bullosa models;
• Contribute to single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses to characterize edited cells and skin organoids, assess cellular states and differentiation, and investigate molecular and spatial responses to genome correction;
• Analyze and interpret experimental data and contribute to scientific presentations, manuscripts and project reporting.

Training can be provided for specific advanced techniques when required. Profile Candidate profile • PhD in life sciences, molecular/cellular biology, genetics, stem-cell biology, skin biology or a related field;

• Strong hands-on experience in molecular and cellular biology;
• Experience with genome editing technologies is highly desirable;
• Experience with skin biology and/or stem-cell culture is an advantage;
• Experience with iPSC culture and manipulation and/or 3D organoid models is highly desirable;
• Experience with sequencing, flow cytometry and quantitative molecular analyses is an advantage;
• Experience with single-cell transcriptomics, spatial transcriptomics and/or analysis of high-dimensional sequencing datasets is an advantage;
• Bioinformatics or data-analysis skills are appreciated.

Skills and personal qualities • Scientific rigor and commitment to reproducibility;

• Ability to work independently while contributing effectively to a multidisciplinary team;
• Strong organizational, communication and problem-solving skills;
• Curiosity, adaptability and motivation to develop innovative therapeutic approaches;
• Good written and spoken English.

Research environment The successful candidate will join a multidisciplinary team of approximately 15 researchers within INSERM UMR 1163 at the Imagine Institute for Genetic Diseases in Paris. The institute offers a highly interactive international environment and access to state-of-the-art core facilities in genomics, bioinformatics, advanced imaging, flow cytometry and preclinical models. The laboratory has established expertise in genetic skin diseases, genome editing, epithelial and stem-cell biology, skin organoids and translational therapeutic development. What we offer • A position within an ANR-funded project at the interface of genome editing, stem-cell biology and translational dermatology;

• Access to advanced technologies and multidisciplinary platforms at the Imagine Institute;
• The opportunity to develop expertise in base editing, prime editing, epithelial stem cells, iPSCs and patient-derived skin organoids;
• A collaborative and internationally oriented research environment with strong opportunities for scientific development.

Application Applicants should send the following documents:

• Curriculum vitae;
• Cover letter describing research experience and motivation for the position;
• Contact details of at least two academic references.