PANDORA欧盟博士网络DC4：评估补体失调如何影响AMD中单核吞噬细胞积聚的博士研究员

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 / required education level / degree: Master Degree or equivalent

Requirements / required education level / discipline: Biological sciences

Requirements / skills: 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)

Requirements / required languages / language: ENGLISH

Requirements / required languages / language level: Excellent

Additional information / benefits: • EU-funded 36-month employment contract under MSCA Doctoral Network rules • Gross salary of approximately 2 800€/month (before taxes and employee social security deductions), as well as mobility allowance and, where applicable, family allowance • Enrolment in the doctoral programme of Sorbonne Université ED394, leading to a PhD degree • Work at the Institut de la Vision, one of Europe's largest integrated centres for research on eye diseases, with state-of-the-art core facilities (iPSC, imaging, transcriptomic, flow cytometry platform) • Participation in PANDORA network-wide training activities: research workshops, complementary skills courses, career perspective workshops and network meetings • Support for conference participation • Intersectoral secondments in academic and industrial partner labs

Additional information / eligibility criteria: Applicants must meet these requirements: • They must not have resided or carried out their main activity (work, studies, etc.) in France for more than 12 months in the 36 months before the recruitment date. Compulsory national service and time spent in refugee status procedures are excluded. • They must not already hold a doctoral degree. • They can be of any nationality.

Additional information / selection process: Application Materials Required: • Curriculum Vitae • 1-page cover letter • Contact details of one or two academic referees

Doctoral candidates will be evaluated on their scientific qualifications, experience, research interests, additional knowledge and skills, and motivation for intersectoral research training. Recruitment follows the open, transparent and merit-based principles of the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers. Shortlisted candidates will be invited to an online interview.

Additional information / info website: https://www.institut-vision.org

Work location / nr job positions: 1

Work location / job organisation institute: Institut de la Vision

Work location / job country: France

Work location / job city: Paris

Work location / job postal code: 75012

Work location / job street: 17 rue Moreau

Hiring contact / organisation institute: Sorbonne Université

Hiring contact / organisation institute type: Higher Education Institute

Hiring contact / division faculty: Medecine Faculty

Hiring contact / country: France

Hiring contact / city: Paris

Hiring contact / postal code: 75012

Hiring contact / street: 17 rue Moreau

Hiring contact / website: http://www.institut-vision.fr

Application / how to apply: e-mail

Application / application email: florian.sennlaub@inserm.fr

EU funding / framework programme: Horizon Europe - MSCA

EU funding / cofund nr job position: 1

EU funding / sesam agreement number: 101312030

Research field / main research field: Biological sciences

Research field / sub research field: Biology

Research field / main research field: Medical sciences

Research field / sub research field: Other

Research field / main research field: Neurosciences

Research field / sub research field: Other

Researcher profile: First Stage Researcher (R1)

Positions: PhD Positions

Contract: Temporary

Job status: Full-time

Application deadline (as exported; timezone unverified): 2026-11-30T22:59:00