PhD Position in EU Doctoral Network "PANDORA" – DC4

Description

Offer Description: The position focuses on "Evaluating how complement dysregulation influences mononuclear phagocyte accumulation in AMD" within the MSCA Doctoral Network PANDORA (Discovering Pathomechanisms and Novel Drug Optimization for AMD). Subretinal mononuclear phagocytes (MPs) build up in the photoreceptor cell layer, a zone normally kept free of immune cells by the immunosuppressive retinal pigment epithelium (RPE). This build-up is a key driver of age-related macular degeneration (AMD). MPs include microglia and monocyte-derived inflammatory macrophages (MoM φ ). Our team has shown that activated MPs evade RPE-mediated clearance. We have also shown that the AMD-linked CFH 402H variant impairs the removal of subretinal MPs independently of its role in the complement system. How complement dysregulation contributes to immune cell accumulation in the subretinal space in AMD remains poorly understood. The PhD student will first map where complement cascade components are found in the human retina. Using multiplexed immunohistochemistry on post-mortem retinal sections from AMD donors and age-matched controls, the student will localise components of the classical, lectin and alternative pathways, their activation products, regulators (CFH and Factor H-related proteins) and receptors. These components will be mapped relative to subretinal MPs, the RPE, photoreceptors and drusen. The student will then study how the Chromosome 1 (Chr1) AMD risk haplotype affects RPE, microglia and MoM φ and their interactions. They will use control and Chr1-risk iPSC-derived cells in a well-defined co-culture system developed in our laboratory. The student will also study the role of plasma-derived Factor H-related proteins (FHR1-5) using depleted human plasma and purified complement factors. Using single-cell and bulk RNA sequencing and proteomics, the student will analyse how complement dysregulation affects: microglia and MoMφ polarisation the interaction of these cells with the immunosuppressive RPE key inflammatory pathways and immune functions in the subretinal microenvironment, in health and in AMD Finally, the student will test whether complement inhibitors (anti-C5, anti-C3) can restore immune balance. The project is supervised by Dr. Florian Sennlaub (Institut de la Vision, Paris) It is carried out in close collaboration with other PANDORA doctoral candidates. Techniques and Training Include: Multiplexed immunohistochemistry on human donor retinal sections (AMD and age-matched controls), whole-slide/confocal imaging and quantitative image analysis Induced pluripotent stem cell (iPSC)-derived RPE, microglia and macrophage models, and immune cell/RPE co-cultures Primary human monocyte isolation and differentiation, and work with human plasma and purified complement factors Single-cell and bulk transcriptomics, and proteomics Flow cytometry, qPCR, western blot, ELISA/multiplex cytokine assays Functional immune assays (phagocytosis, migration, survival/clearance) Requirements: Research Field Biological sciences » Biology Education Level Master Degree or equivalent Skills/Qualifications Essential Skills/Qualifications: Solid knowledge of cellular and molecular biology and/or immunology Excellent written and oral English proficiency Strong motivation for research on retinal degeneration and neuroinflammation Ability to work both in a team and independently Preferred Qualifications: Hands-on experience in cell culture (ideally primary immune cells or iPSC-derived cells) and flow cytometry Experience with immunohistochemistry/immunofluorescence and image analysis Background in innate immunity, macrophage/microglia biology and the complement system Interest in, or basic experience with, omics data analysis Language: Excellent English (French not required) Languages ENGLISH Level Excellent Additional Information: Benefits EU-funded 36-month employment contract under MSCA Doctoral Network rules Gross salary of approximately 2 800€/month (bef

Secteurs

Source

Source: euraxess.ec.europa.eu