MSCA-DN PhD in pharmacological therapy for leukodystrophies (Rome, IT)

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.