PhD Position in EU Doctoral Network \"PANDORA\"

Institut de la vision; Paris; Hybrid; EUR 28,000 - 34,000; Full time

Job summary

Institut de la Vision in Paris hosts a MSCA Doctoral Network PhD project titled “Evaluating how complement dysregulation influences mononuclear phagocyte accumulation in AMD.” The student will map complement components in the human retina and study interactions with RPE, microglia and MoM using post-mortem tissue, iPSC-derived cells and state-of-the-art analyses.

The program includes an intersectoral dimension within the PANDORA network, 36-month contract, and enrollment in Sorbonne Université

Qualifications

• Solid knowledge of cellular and molecular biology and 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.

Responsibilities

• Map complement cascade components in the human retina.
• Localise activation pathways relative to subretinal MPs and RPE.
• Study Chr1 AMD risk haplotype effects using control and iPSC-derived cells.
• Use single-cell and bulk RNA sequencing and proteomics to analyse complement dysregulation.

Skills

Immunology research

Cell culture experience

English proficiency

Teamwork independence

Education

Master’s degree in life sciences

Job 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). 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.

It is carried out in close collaboration with other PANDORA doctoral candidates.

Missions

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 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 MoM 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.

Skills required

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)

Education and experience

Education Level:Master's Degree or equivalent in life sciences, biology, immunology, neurobiology or biomedical sciences

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.

Specific working conditions

• 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

Selection process

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.

Deadline : 26/11/30 , 6:00 p.m. (Europe/Paris)