Cytotoxic CD8+ T Cells as Early Drivers of Dopaminergic Neuronal Death in Parkinson’s Disease VHIR is seeking an outstanding and highly motivated postdoctoral researcher to apply for a Marie Sklodowska‑Curie Postdoctoral Fellowship and join the Neurodegenerative Disorders Research Group.

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 .

Background Parkinson’s disease (PD) is characterised by the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), yet the events that initiate their death remain unresolved. The host laboratory has generated post‑mortem human evidence that places cytotoxic CD8+ T cells at the very beginning of this process.

In a systematic analysis of SNpc tissue spanning the full neuropathological spectrum of PD, CD8+ T cells were found to infiltrate the substantia nigra before α‑synuclein aggregation or neuronal loss is detectable. At the earliest presymptomatic Braak stages, when α‑synuclein pathology is still confined to the olfactory bulb and brainstem, the SNpc already shows robust infiltration of CD8+ T cells—including granzyme B‑expressing tissue‑resident memory subsets—many of which make direct physical contacts with tyrosine hydroxylase‑positive dopaminergic neurons. CD4+ T cells do not show a comparable pattern of nigral infiltration or neuronal contact.

These findings, published in Brain (Galiano‑Landeira et al., 2020), establish that a cytotoxic T cell response against dopaminergic neurons is one of the earliest detectable events in PD, raising the hypothesis that it may trigger, rather than merely accompany, the subsequent cascade of protein aggregation and neuronal death. The intrinsic oxidative burden of dopaminergic neurons, due to dopamine metabolism, mitochondrial complex I insufficiency and catecholamine auto‑oxidation, generates modified intracellular proteins and potential neo‑antigens that may be presented via MHC class I, making stressed dopaminergic neurons immunologically visible to antigen‑specific CD8+ T cells. Neuromelanin, the dark intraneuronal pigment that accumulates with age, acts as a marker of this oxidative state.

Neurons with the greatest neuromelanin load are those that degenerate earliest and most severely. Post‑mortem data from the host laboratory show that CD8+ T cells preferentially contact neuromelanin‑laden neurons, suggesting that oxidative stress‑associated antigenicity may determine selective vulnerability.



To interrogate this hypothesis in a tractable experimental system, the lab has developed unique rodent models in which dopaminergic neurons accumulate intraneuronal neuromelanin and replicate the oxidative microenvironment of human SNpc neurons.

Preliminary data in these animals show CD8+ T cell infiltration and contacts with neuromelanin‑accumulating neurons, mirroring human findings and providing a platform to dissect the causal role of CD8+ T cells in dopaminergic neurodegeneration in vivo.

Objective

Establish the causal and temporal relationship between CD8+ T cell infiltration and the earliest events of dopaminergic neuronal stress, quantifying markers of neuronal stress, microglial activation, and the spatial distribution of infiltrating CD8+ T cells, and applying spatial transcriptomics at the earliest detectable time point.

Determine whether CD8+ T cells are necessary effectors of dopaminergic neurodegeneration through antibody‑mediated depletion at two critical stages: the earliest time point with neuronal stress but no overt loss, and the stage of maximal infiltration and neurodegeneration.

Characterise the phenotype, clonal architecture, and antigen specificity of SNpc‑infiltrating and CSF‑derived CD8+ T cells using full‑length single‑cell immunogenomics (scRNA‑seq + scTCR‑seq).

Our Group The Neurodegenerative Diseases Research Group at VHIR is led by Dr.

Miquel

Vila (ICREA Professor) and is part of CIBERNED and the Aligning Science Across Parkinson's Collaborative Research Network (ASAP‑CRN). The host institution, the Vall d'Hebron Institut de Recerca (VHIR), is the research arm of Vall d'Hebron University Hospital, a leading European centre for clinical and translational research. Core research facilities include a High Technology Unit, Statistics and Bioinformatics Unit, Lab Animal Service, Biobank, and Clinical Research Support Unit, and VHIR is a member of EATRIS and ECRIN. The group’s methodology spans in vivo rodent neurobiology, human post‑mortem and patient tissue analysis, multiplex immunofluorescence, spatial transcriptomics, bulk and single‑cell RNA sequencing, single‑cell TCR sequencing, and metatranscriptomics, with active international collaborations in neuropathology, neuroimmunology, and computational biology.

Main responsibilities and duties

Work with experimental platforms, including neuromelanin‑accumulating rodent models, human post‑mortem SNpc tissue, multiplex immunofluorescence, spatial transcriptomics, scRNA‑seq, scTCR‑seq, and metatranscriptomics.

Receive training in experimental neuroimmunology, translational PD research, and single‑cell genomics within a highly collaborative international environment.

Education and qualifications

Required

Applicants must hold a PhD degree or have successfully defended their thesis before the call deadline (09/09/2026).

Required

Applicants must comply with the mobility rule,



meaning they must not have resided or carried out their main activity (work/studies) in the host country for more than 12 months during the 36 months prior to the call deadline.

Required

Proficiency in English (written and spoken).

Desirable

Formal training in bioinformatics or computational biology, evidenced by a postgraduate degree, specialisation diploma, or completion of a recognised course programme.

Experience and knowledge

Required

A maximum of 8 years of postdoctoral research experience by the call deadline (typically candidates who obtained their PhD on or after 10/09/2018, with possible extensions).

Required

Demonstrable hands‑on experience in standard neuroimmunology techniques, including immunohistochemistry or immunofluorescence on brain tissue, flow cytometry, or immune cell isolation and culture from CNS or peripheral compartments.

Required

Strong analytical and problem‑solving skills with capacity for independent scientific thinking.

Desirable

Experience with spatial transcriptomics or protein multiplexing platforms.

Desirable

Familiarity with bioinformatics pipelines for single‑cell and bulk data analysis.

Desirable

Experience with animal models.

Working conditions, remuneration, contract type and start date will be established according to the applicable MSCA Postdoctoral Fellowship conditions and VHIR regulations.

What can we offer?

Incorporation into the Vall d’Hebron Research Institute (VHIR), a public sector institution that promotes and develops biomedical research, innovation and teaching at Vall d'Hebron University Hospital.

A dynamic scientific environment of excellence, where cutting‑edge biomedical projects are continuously developed.

Continuous learning and career development pathways.

Healthy offering– “Feel Good, Feel VHIR”: a wellbeing programme offering a variety of activities to help staff thrive physically, mentally, and socially, organised around four pillars—Feel Well, Feel Connected, Feel Empowered, Feel Welcomed.

International mobility support (Welcome Services): city information, guidance on required procedures, access to the International Welcome Desk, family support and assistance with finding accommodation.

Deadline to apply: 31-07-2026 VHIR embraces Equality and Diversity. As reflected in our values, we work toward ensuring inclusion and equal opportunity in recruitment, hiring, training, and management for all staff within the organisation, regardless of gender, civil status, family status, sexual orientation, gender identity or expression, religion, age, functional diversity or ethnicity.

Information on Personal Data Protection Data Controller: Fundació Hospital Universitari Vall d’Hebron Institut de Recerca‑VHIR‑

Purpose: Personnel selection. Legal Basis: Your consent. Data retention period: One year. If you are selected, as long as the employment relationship is in force and legal responsibilities may arise.

Data sharing: Does not occur, except for communications necessary to fulfil the purpose and those required by law to public and private bodies.

Rights: You can access, rectify, delete, object to, and limit the processing of data, as well as request data portability where applicable, by contacting [email protected]. DPO: [email protected]. More information can be found here.

Data Protection Authority: APDCAT

📌 VHIR-MSCA-.008_Postdoctoral Fellowship (Neurodegenerative Disorders) (Madrid)
🏢 Vall d’Hebron Institute of Research (VHIR) - Vall d'Hebron Institut de Recerca
📍 Madrid