MSCA-DN PhD position in liquid biomarkers for leukodystrophies (Tübingen, GE)

POLARIS is a European Marie Skłodowska-Curie Doctoral Network focused on accelerating therapy development for leukodystrophies: rare genetic disorders affecting the brain's white matter. The network aims to strengthen the full translational pathway, from understanding disease mechanisms and developing disease models to preclinical therapy testing, clinical readiness and patient-informed treatment priorities.

To achieve this, POLARIS brings together expertise in leukodystrophy biology, advanced disease models, therapeutic innovation, biomarker development, clinical translation, patient engagement, and ethical, regulatory and health-economic aspects of therapy development. The network will train a cohort of doctoral candidates in an international and interdisciplinary environment, combining academic research, industry-based preclinical development, secondments, network-wide training and transferable-skills development.

The PhD
Leukodystrophies are rare genetic disorders affecting the white matter of the central nervous system. With the introduction of newborn screening and the first gene therapies, affected children can increasingly be identified and treated before symptom onset. However, minimally invasive biomarkers are still needed to support early diagnosis, monitor disease progression and assess treatment response.

In this PhD project, you will develop and validate liquid biomarkers for leukodystrophies by integrating multi-omics data from patient plasma and iPSC-derived human disease models. You will investigate disease-related molecular signatures using metabolomics, lipidomics, proteomics and genomics, and combine these data using statistical and machine-learning approaches. Established markers such as neurofilament light chain (NfL) and GFAP will provide a biological reference point for identifying disease-specific biomarkers.

A central part of the project is the use of iPSC-derived models, including oligodendrocytes, astrocytes, neurons and myelinating organoids. Depending on your background and interests, the project can focus more on establishing and characterising these models or on the computational integration of multi-omics data. Both aspects will be closely connected within the research team.

The resulting biomarker panel will aim to support newborn-screening follow-up and monitoring of emerging therapies, including gene and lipid-nanoparticle therapies.

Planned secondments will provide experience in omics data generation and biomarker development in an industrial and regulatory setting, including a placement at Orchard Therapeutics. A secondment with the European Leukodystrophy Association (ELA) will offer the opportunity to engage with patients and families and learn about the priorities of affected communities.

The position is based in Tübingen, Germany, with academic enrolment through the Eberhard Karls University of Tübingen. You will pursue a PhD degree in a relevant discipline.

You will contribute to the development and validation of liquid biomarkers for leukodystrophies. You will work with iPSC-derived disease models and patient samples, generate and analyse multi-omics data, and help identify biomarkers that can support diagnosis, disease monitoring and treatment evaluation.

You will work closely with researchers in human genetics, computational biology and clinical neurology and collaborate with POLARIS partners across Europe. Through planned secondments, you will gain experience in omics research, biomarker development and patient engagement.

You will have the opportunity to shape the focus of your research according to your background and interests, with an emphasis either on iPSC-based disease modelling or on computational analysis and integration of multi-omics data.