MSCA-DN PhD in pharmacological therapy for leukodystrophies

The POLARIS training network

POLARIS is a European Marie Skłodowska-Curie Doctoral Network focused on accelerating therapy development for leukodystrophies: rare genetic disorders affecting the brain white matter. The network aims to strengthen the full translational pathway from disease mechanism and model development 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

For this position, the recruiting organisation is the Istituto Superiore di Sanità (ISS) in Rome, Italy. You will be employed by the ISS and embedded in the international and interdisciplinary POLARIS consortium. You will be supervised by Dr Elena Ambrosini and benefit from disease-specific expertise from Dr Angela Lanciotti and Dr Maria Stefania Brignone at the Department of Neuroscience of the ISS, as well as academic support from Prof. Maria Egle De Stefano at Sapienza University of Rome.

This PhD project focuses on the preclinical evaluation of pharmacological therapies for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare leukodystrophy. You will use human in vitro models, including astrocytes and brain organoids generated from induced pluripotent stem cells (iPSCs) of people with MLC and healthy controls.

You will investigate disease-relevant phenotypes using cellular, molecular, biochemical, imaging and omics approaches. These models will support compound screening and the evaluation of potential therapies.

The project combines stem cell-based disease modelling, neuroscience and translational research. Through planned secondments, you will also gain experience with MLC animal models and computational chemistry approaches for identifying drug repurposing candidates.

You will contribute to different stages of the research project. Your work will include:

• Developing and using human in vitro models derived from patient and control iPSCs.
• Investigating disease-relevant cellular and molecular mechanisms using a range of experimental techniques.
• Applying imaging, biochemical and omics approaches to characterise disease phenotypes.
• Supporting compound screening and evaluating the efficacy of potential pharmacological therapies.
• Working with researchers across the POLARIS consortium and contributing to the network-wide training programme.

During planned secondments, you will broaden your expertise in preclinical drug development. At Amsterdam UMC in the Netherlands, you will receive training in MLC animal models for the preclinical evaluation of pharmacological therapies under the supervision of Dr Rogier Min. At the National Research Council of Italy (CNR) in Cagliari, you will learn computational chemistry approaches to identify drug repurposing compounds based on pathological pathways identified in patient-derived models.

You will be based at the ISS in Rome and academically enrolled at Sapienza University of Rome. You will pursue a PhD degree in Cell and Developmental Biology.

Requirements

We are looking for a motivated researcher who is interested in translational neuroscience, rare diseases and the development of pharmacological therapies. You bring:

• A Master's degree in Life Sciences, preferably in Neuroscience.
• Experience with molecular biology and imaging techniques and with developing or using in vitro cellular models.
• An interest in using human cellular models to investigate disease mechanisms and evaluate potential therapies.
• Strong analytical and problem-solving skills, with the ability to critically assess experimental results and adapt your approach when needed.
• Good communication and interpersonal skills and the ability to work effectively in an interdisciplinary and international research environment.

You work accurately and reproducibly, pay attention to detail and can plan and organise complex experimental work. You will collaborate with colleagues at the ISS and with researchers across the POLARIS consortium.

Fluency in written and spoken English is essential.

Eligibility criteria

Important, strict eligibility criteria according to MARIE SKLODOWSKA CURIE programs apply to applicants:

• You must not already hold a doctoral degree.
• At the time of the application deadline, you must have a Master's degree and must not have resided or carried out your main activity (work, studies, etc.) in Italy for more than 12 months in the three years prior to the contract start date.
• You will participate in the network-wide training programme of POLARIS, which includes (international) training activities and planned secondments with POLARIS partner organizations throughout the EU.

Conditions of employment

• A full-time, 3-year employment contract with ISS, under the agreement with Sapienza University of Rome;
• A salary, mobility allowance, and benefits in accordance with the applicable MSCA Doctoral Network and host organisation rules;
• Full integration into the international POLARIS Doctoral Training Network;
• Access to network-wide training activities, secondments, and transferable skills development;
• A challenging and highly translational research project at the interface of cellular and molecular neuroscience, rare disease biology, and preclinical drug development;
• A collaborative and interdisciplinary research environment;
• A supportive and inclusive workplace with opportunities for scientific and professional development.

Employer

The Istituto Superiore di Sanità (ISS), the Italian National Institute of Health, is Italy's leading public research institution in biomedicine and public health. As the technical and scientific body of the Italian National Health Service, the ISS combines research and institutional activities across a wide range of scientific disciplines.

You will join the Department of Neuroscience, which conducts research into both common and rare neurological disorders, including leukodystrophies. The department investigates disease mechanisms, develops approaches for early diagnosis and identifies new therapeutic targets and treatment strategies. An important part of its work is translating promising research findings into applications that can improve patient care and quality of life.

You will also be part of the international POLARIS doctoral network. You will work with researchers from different scientific disciplines and collaborate with academic and industry partners across Europe. Through secondments, network-wide training and transferable-skills development, you will build experience beyond your own research project and develop an international research network.

POLARIS is committed to open, transparent and merit-based recruitment. We value diversity and welcome candidates with different backgrounds, perspectives and experiences.

Additional information

The application deadline is 5 October 2026. We aim to select the final candidate in October/November 2026.

Applicants may, where appropriate and in line with the recruitment procedure, also be considered for other POLARIS doctoral candidate positions that better match their profile and interests. You can highlight up to two additional POLARIS projects of interest in your application letter. This does not replace your application to the primary position, but helps the consortium identify potential alternative matches where relevant.

Would you like to know more about this PhD position? For substantive information about the vacancy, please contact dr Elena Ambrosini via elena.ambrosini@iss.it.

Acquisition in response to this vacancy will not be considered.