Postdoctoral position on mitochondrial inflammation (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 A postdoctoral position is available in the team of Dr Alice Lepelley at the Institut Imagine (Paris) to study mitochondrial nucleic acid immunogenicity and neuroinflammation in genetic diseases. The Institut Imagine (IHU, ‘Institut Hospitalo-Universitaire', Inserm U1163) is a recently established research structure located next to the Necker Children's Hospital (Paris). Its research laboratories are focused on understanding the molecular mechanism of genetic diseases that affect the adaptive and innate immune systems, the nervous system, stem cell differentiation, kidney physiology, metabolism, etc. Imagine offers a unique environment in which clinical and basic science synergize to produce major contributions in clinical and translational research. Imagine is internationally recognized for its high-quality, well-published, multi-disciplinary outputs. Description/activities : The Laboratory of Neurogenetics and Neuroinflammation is focused on the study of the molecular and cellular basis of the type I interferonopathies, genetic diseases characterised by pathogenic chronic upregulation of type I interferon signalling. Understanding of these diseases has highlighted the critical nature of innate immune system tolerance to self-nucleic acids, which can activate innate sensors and thereby trigger an abnormal interferon response, in particular in the central nervous system (CNS). Notably, when released from the mitochondrial compartment, mitochondrial nucleic acids are very potent ligands of innate immune receptors. Study of this process is of high scientific interest, with basic and translational implications for research on autoimmunity and neurodegeneration. We have recently linked cytosolic mtRNA and mtDNA sensing to elevated IFN-I signalling in PNPT1, ATAD3A and MTPAP -related mitochondrial disease (PMID: 34387651, 30046113, ). The postdoctoral researcher will study the mechanisms controlling mitochondrial nucleic acid immunogenicity in the context of disease-causing mutations in mitochondrial proteins, e.g. relating to mtRNA processing, mtDNA localisation, mitochondrial membrane structure, mitophagy. The project will involve the use of patient primary cell cultures, human cell lines and iPSC-derived CNS models, in combination with advanced fluorescence microscopy (confocal, STED), silencing screens, CRISPR/cas9 gene editing, and multiple transcriptomic analyses (including nanopore and Pacbio long read sequencing and sequencing of immunoprecipitated RNA), in addition to standard molecular biology, biochemistry, flow cytometry. Profile Competencies required: • We are looking for a highly motivated postdoctoral researcher with solid experience of molecular and cellular biology and mitochondrial studies;

• The candidate should have a PhD in a relevant field;
• Expertise in iPSC culture and differentiation into neural cells and/or bioinformatics analyses would be an advantage;
• The candidate should be driven, organized, innovative, able to work in autonomy, to lead the project, to optimise and/or develop new study systems, to communicate and work efficiently with the team, platforms and external collaborators;
• The candidate will participate in trainee supervision and contribute to scientific presentations, manuscripts and project reporting;
• The candidate should be fluent in English.

Contract: The position is offered for one year with the possibility for extension. The position is available from December 2026, with salary depending on experience. Application: Please send a concise cover letter with a summary of previous and current research activity, detailed curriculum vitae, and the contact information for two references (to be contacted only with the express permission of the candidate).