2 Phd Positions

**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**: - MSCA-DN-2023 Cilia-AI: Cutting-Edge Research & Training Programme_ Are you passionate about biomedical research or cell biology? Ready to make groundbreaking contributions to understanding ciliopathies through innovative machine learning approaches? Join the Cilia-AI consortium, and embark on an unparalleled research journey. **Two open positions at the Institut**_Imagine_**: - Cilia in Organ Development and Physiology _(DC8) ;_ - Ciliary Molecules: Structure and (Dys-) Function_ (DC10)._ **Position details**: DC8: Phenotypic characterization and drug discovery in zebrafish models of renal ciliopathies Supervisor: Dr Alexandre Benmerah ; Master degree: Life sciences, Biomedical science, Biology or related field ; Experience with zebrafish would be beneficial ; Anticipated starting date: September 2025. DC10: Impact of IFT variants in renal ciliopathies Supervisor: Dr Sophie Saunier ; Master degree: Life sciences, Biomedical science, Biology or related field ; Anticipated starting date: September 2025. **Project descriptions**: DC8: High-content microscopy and AI-based tools for phenotypic characterization and drug discovery in zebrafish models of renal ciliopathies DC10: Impact of IFT variants in renal ciliopathies using AI-based tools Variants in IFT genes are a frequent cause of renal ciliopathies, such as nephronophthisis (NPH) and autosomal dominant polycystic kidney disease (PKD). Furthermore, recent data from P5-Imagine indicates the presence of modifier alleles in IFTA genes in the context of NPHP1-associated NPH. We will study how these variants affect the structure and function of the IFT complex using deep-learning algorithms. **(1)**The severity of mutations will be assessed through Alpha missense, and their impact on structure and interactions will be examined using Alphafold modeling (coll. P4-UHEI) as well as through biochemical approaches (coll. P3-AU). **(2)**The most relevant alleles will be stably expressed as tagged forms in kidney cell lines invalidated for the respective IFTA subunit by CRISPR-Cas9. Their ability to rescue the phenotype associated with NPHP1 (cilia defects, transcriptomic profiling, etc) will also be investigated in NPHP1-invalidated cells. The impact on ciliogenesis and ciliary composition will be examined using an AI-based image analysis system (AP5-Medetia) and proximity labeling (coll. P1-RUMC), respectively. **(3)**In parallel, additional causative and modifier variants will be sought in ciliopathy cohorts from internal databases (> 2000) and existing ones. The genetic and molecular profiles will be linked to clinical phenotypes and disease progression using AI methodology such as patient similarity network (PSN) integration, will use PSN framework to integrate diverse data types and to identify biological features characteristic of disease with the aim for clinical risk factor assessment. **Profile**: Background in biomedical sciences, cell biology, or a related field. Researcher profile: First stage researcher (R1) **Benefits**: Have — at the date of recruitment — a Master’s degree in (see DC positions) Life Science, Biomedical Science, Cell-, Molecular-, Developmental-Biology. **Trans-national mobility**: The applicant — at the date of recruitment — should not have resided in the country where the research training takes place for more than 12 months in the 3 years immediately prior to recruitment, and not have carried out their main activity (work, studies, etc.) in that country. For refugees under the Geneva Convention (1951 Refugee Convention and the 1967 Protocol), the refugee procedure (i.e. before refugee status is conferred) will not be counted as ‘period of residence/activity in the country of the beneficiary’. Be able to communicate (speaking and writing) fluently in English. **How to apply**: - a 1-page letter of motivation regarding the position(s) as well as the Cilia-AI network ; - a detailed CV, including education, work experience, skills, dissertations, research interests, career objectives, and names and contact details of two referees, that can include the supervisor of the master thesis, willing to provide confidential letters of recommendation ; - completed preference form indicating the PROJECT(S) you are interested in (max 3; DC2,..., DC13, see below) ; - a transcript of the master studies’ grades (including the overall grade and an explanation of the grading system) and the _abstract _of the master’s