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 . Full eligibility details: MSCA Postdoctoral
Fellowships 2026 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. What
renders SNpc dopaminergic neurons specifically vulnerable to this
CD8+ attack remains an open and fundamental question. These neurons
operate under conditions of chronic and exceptionally high
oxidative stress, arising from dopamine metabolism, mitochondrial
complex I insufficiency, and sustained catecholamine
auto-oxidation. This intrinsic oxidative burden generates modified
intracellular proteins and potential neo-antigens that may be
processed and presented via MHC class I, making stressed
dopaminergic neurons immunologically visible to antigen-specific
CD8+ T cells. Neuromelanin—the dark intraneuronal pigment that
accumulates progressively with age as a by-product of catecholamine
oxidation, uniquely abundant in human SNpc neurons—is a
histological indicator of this sustained oxidative state. The
neurons that accumulate the most neuromelanin are precisely those
that degenerate earliest and most severely in PD, and post-mortem
data from the host laboratory show that CD8+ T cells preferentially
contact neuromelanin-laden neurons, pointing to oxidative
stress-associated antigenicity as a potential determinant of
selective vulnerability. To interrogate this hypothesis in a
tractable experimental system, the host laboratory 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 that CD8+ T cells infiltrate the SNpc and establish
contacts with neuromelanin-accumulating neurons, closely mirroring
the human post mortem findings, and providing the first
experimentally tractable platform to dissect the causal role of
CD8+ T cells in dopaminergic neurodegeneration in vivo. Objective




The overarching goal of this project is to establish whether
cytotoxic CD8+ T cells initiate, amplify, or are required effectors
of dopaminergic neuronal dysfunction and death in PD. The project
builds directly on the host laboratory’s post-mortem human findings
and uses unique rodent models that replicate the oxidative
microenvironment of human SNpc neurons to interrogate CD8+ T
cell-mediated pathology in vivo. Objective 1: Establish the causal
and temporal relationship between CD8+ T cell infiltration and the
earliest events of dopaminergic neuronal stress. High-resolution
immunofluorescence will quantify markers of neuronal stress
(tyrosine hydroxylase downregulation, mitochondrial and lysosomal
dysfunction, protein aggregation), microglial activation (Iba1,
CD68), and the extent, activation state, and spatial distribution
of infiltrating CD8+ T cells. Spatial transcriptomics will be
applied at the earliest time point at which CD8+ infiltration is
detectable, enabling in situ reconstruction of the neuron–immune
transcriptional interactome at the onset of the cytotoxic response.
Objective 2: Determine whether CD8+ T cells are necessary effectors
of dopaminergic neurodegeneration through antibody-mediated
depletion at two critical stages: (a) the earliest time point
showing tyrosine hydroxylase downregulation without overt neuronal
loss, to test whether CD8+ T cells drive the transition from
dysfunction to death; and (b) at the stage of maximal infiltration
and neurodegeneration, to assess whether their removal can halt
ongoing injury. Outcomes will include dopaminergic neuron counts,
neuronal stress markers, and microglial activation state. Objective
3: Characterise the phenotype, clonal architecture, and antigen
specificity of SNpc-infiltrating and CSF-derived CD8+ T cells.
Full-length single-cell immunogenomics (scRNA-seq + scTCR-seq) will
be performed on CD8+ T cells isolated from the SNpc and CSF at the
most informative time points. This will define cytotoxic,
exhausted, and tissue-resident memory states; reveal clonally
expanded TCR repertoires indicative of antigen-driven selection;
and generate convergent CDR3 motifs as candidates for computational
antigen prediction. Findings will be interpreted in light of the
human post-mortem TCR data generated in parallel by the host
laboratory. Our Group The Neurodegenerative Diseases Research Group
at VHIR is led by Dr. Miquel Vila (ICREA Professor) and is part of
CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades
Neurodegenerativas) and the Aligning Science Across Parkinson's
Collaborative Research Network (ASAP-CRN), providing access to a
broad national and international collaborative framework in basic
and clinical PD research. The host institution is the Vall d'Hebron
Institut de Recerca (VHIR), the research arm of Vall d'Hebron
University Hospital — the largest hospital of the Catalan Institute
of Health and the main hospital of Barcelona — and a recognised
leader in clinical and translational research at the European
level, part of the Vall d'Hebron Barcelona Hospital Campus, a
general-leading health park where research, clinical care, teaching,
and innovation go hand in hand. VHIR is a CERCA centre, accredited
by the Instituto de Salud Carlos III (ISCIII), and affiliated to
the Autonomous University of Barcelona (UAB). Core research
facilities available to fellows 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, providing access to pan-European research
infrastructures. The group’s methodological portfolio 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: The fellow will have work with
experimental platforms, including neuromelanin-accumulating rodent
models, human post-mortem SNpc tissue spanning the full
neuropathological spectrum of PD, multiplex immunofluorescence,
spatial transcriptomics, scRNA-seq, scTCR-seq, and
metatranscriptomics. 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) 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. 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
program. Experience and knowledge: Required: Applicants must have a
maximum of 8 years of postdoctoral research experience by the call
deadline. This means candidates are generally eligible if they
obtained their PhD on or after 10/09/2018 (possible extensions may
apply, e.g. parental leave or long-term illness). 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. Strong analytical and
problem-solving skills with capacity for independent scientific
thinking Desirable: Experience with spatial transcriptomics or
protein multiplexing platforms. Familiarity with bioinformatics
pipelines for single-cell and bulk data analysis. 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 (HUVH), the largest hospital in Barcelona and
the largest within the Catalan Institute of Health (ICS) . 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” : VHIR’s wellbeing programme offers a variety of
activities to help staff thrive—physically, mentally, and socially.
Through four pillars—Feel Well, Feel Connected, Feel Empowered,
Feel Welcomed—it fosters health, growth, and community.
International mobility support (Welcome Services) : we aim to make
your arrival in Barcelona smooth and pleasant by providing 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 and 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 fulfill 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) (Cataluña)
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