Functional validation of genetic variants in paediatric inborn errors of immunity

The Infection and Immunity in Paediatric Patients Research Group at the Vall d'Hebron Research Institute (VHIR), Barcelona, is seeking an outstanding postdoctoral researcher interested in developing competitive applications for the next Marie Sklodowska-Curie Postdoctoral Fellowships (MSCA-PF).

Marie Skłodowska-Curie Actions – Postdoctoral Fellowships (MSCA-PF)

The Marie Skłodowska-Curie Postdoctoral Fellowships (MSCA-PF) are part of the Horizon Europe programme and support postdoctoral researchers in developing an original research and innovation project through international mobility.

The programme aims to strengthen researchers’ careers through excellent science, international collaboration and interdisciplinary experience, while fostering integration in both academic and non-academic environments. The MSCA-PF call is highly competitive and represents an excellent opportunity to attract international talent and support researchers in consolidating their scientific careers through an ambitious mobility-based fellowship.

The 2026 call closes on 09/09/2026 (17:00 Brussels time). For candidates applying to a European Postdoctoral Fellowship, the fellowship duration is from 12 to 24 months.

Full eligibility details: MSCA Postdoctoral Fellowships 2026

Background

Next-generation sequencing has improved the diagnosis of inborn errors of immunity (IEI), but it has also created a growing bottleneck: candidate variants and variants of uncertain significance (VUS) that cannot be translated into diagnosis, counselling or targeted treatment without functional evidence. This is especially relevant in children with severe infection susceptibility, immune dysregulation, cytopenias, autoinflammation, combined immunodeficiency or complex syndromic presentations.

The project will build on the pediatric IEI programme, the Advanced Immunology Testing Laboratory and the joint laboratory activity established between the Infection and Immunity in Pediatric Patients Research Group (I2P2-RG) and the Translational Immunology at VHIR. It will combine deep clinical phenotyping, advanced immunophenotyping, primary human cell assays, engineered cellular systems and selected in vivo models to move from genomic suspicion to experimentally supported pathogenicity.

Objective

• Establish a structured VUS validation pipeline integrating phenotype, segregation, genomic/structural variant analysis, transcript-level evidence, immune profiling and ACMG/AMP-oriented interpretation.

• Develop patient-derived functional assays using PBMCs, lymphocyte subsets, neutrophils and/or fibroblasts, with readouts adapted to the suspected pathway.

• Interrogate priority pathways relevant to IEI, including JAK/STAT, NF-kB, PI3K-AKT/mTOR, lymphocyte activation, antibody deficiency and oxidative burst/host-defence mechanisms.

• Generate complementary human models, including stimulated primary cells, immortalised or CRISPR-edited cell systems, rescue/overexpression experiments and multi-omics readouts where appropriate.

• Use selected animal or preclinical models, according to biological plausibility and feasibility, to assess immune development, infection susceptibility or inflammatory phenotypes in vivo.

• Translate validated results into variant reclassification, genotype-phenotype refinement, diagnostic reporting and precision therapeutic decisions for children with IEI.

The Group

Research Group, led by Dr Pere Soler-Palacín, focuses on paediatric infectious diseases and immunodeficiencies, with a strong translational orientation from bedside phenotyping to laboratory validation and personalised management. The group studies congenital errors of immunity, severe and unusual infections, immune dysregulation, biomarkers, targeted therapies and diagnostic innovation.

The group coordinates an Advanced Immunology Testing Laboratory and works in a shared laboratory ecosystem with the Translational Immunology group at VHIR. This setting provides access to well-characterised paediatric IEI cohorts, clinical samples, immunophenotyping platforms, molecular genetics, bioinformatics, biobank resources, animal facilities and preclinical/functional validation support. In the last year, the group reported 48 publications, 72.9% in Q1 journals, 140 citations, 12 ongoing projects and 16 active clinical trials.

Main responsibilities and duties:

• Collaborate with the Translational Immunology group, creating a joint human immunology/genetics laboratory setting for IEI variant prioritisation and functional validation Methodological publications, validated reusable code or data models, and a roadmap for clinically safe deployment of IEI screening tools.
• Focus on primary immune-cell assays, advanced flow cytometry and phospho-flow, cytokine and Luminex assays, ELISA, Western blotting, transcript/cDNA analysis, cell culture, genome editing, structural variant interpretation or animal/preclinical modelling.
• Validate functional workflows, mechanistic studies of selected genes or pathways, publications linking genotype to immune phenotype, and clinically actionable evidence for diagnosis and treatment.