MSCA-DN PhD in gene correction for vanishing white matter & MLD (Zurich, CH)

POLARIS doctoral network 

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

For this position, the recruiting organisation is the University of Zurich (UZH) in Zurich, Switzerland. The selected candidate will be employed by UZH and become part of the POLARIS consortium, with academic supervision and genome-editing expertise provided by Prof. Gerald Schwank at the Institute of Pharmacology and Toxicology.

The Institute of Pharmacology and Toxicology at the University of Zurich conducts research at the interface of molecular medicine, pharmacology and therapeutic innovation. The Schwank laboratory develops and applies genome-editing technologies to understand and treat genetic diseases, with a focus on precise and durable therapeutic genome engineering.

Prof. Gerald Schwank’s team develops programmable genome-editing systems and delivery strategies for therapeutic applications. By combining expertise in genome-editor engineering, molecular biology and translational model systems, the team aims to advance safe and effective genetic medicines for severe inherited diseases.

You will develop gene-editing strategies for two leukodystrophies: vanishing white matter disease (VWM) and metachromatic leukodystrophy (MLD). You will work at the interface of genome editing, targeted delivery and preclinical disease modelling, with the aim of advancing new therapeutic approaches.

Your research will focus on:

• Developing gene-editing strategies for VWM and MLD, including precise gene correction and whole-gene insertion.
• Developing targeted delivery approaches using lipid nanoparticles (LNPs) to reach the relevant therapeutic target cells: glial cells in the brain for VWM and hematopoietic stem and progenitor cells for MLD.
• Evaluating the efficacy, durability and safety of different editing approaches in relevant cellular and preclinical disease models.
• Assessing potential safety risks, including off-target genomic integration and long-term tolerability.
• Working across research environments through planned secondments at Amsterdam UMC and InnoSer. At Amsterdam UMC, you will gain experience with phenotypic assays in VWM and MLD models, while at InnoSer you will work on the phenotyping of leukodystrophy mouse models. 

Your academic research will be embedded within the Institute of Pharmacology and Toxicology at the University of Zurich, under the supervision of Prof. Gerald Schwank. The anticipated PhD defence will take place at the University of Zurich.

We are looking for a motivated candidate who is interested in therapeutic genome editing, rare-disease research and translational science. You bring:

• A Master’s degree in molecular biology, biotechnology, biomedical sciences, genetics, bioengineering or a related life-sciences field.
• Experience in molecular biology, genome editing, nucleic-acid delivery, mammalian cell culture or hematopoietic stem and progenitor cells, gained through internships or research projects.
• Experience with CRISPR-based editing, cloning or sequencing-based analysis of editing outcomes is advantageous.
• Experience with lipid nanoparticles or viral-vector delivery is advantageous.
• Experience with animal models, animal-welfare principles and robust experimental design is advantageous.
• A strong interest in developing new therapeutic approaches for rare genetic diseases.
• An accurate and reproducible way of working, with a strong eye for detail and the ability to plan and organise complex experimental work.
• An analytical mindset, good communication skills and the ability to collaborate across different research environments.
• The ability and willingness to work in an interdisciplinary and international research environment, collaborating with colleagues at UZH and across the POLARIS consortium.

Fluency in English, both written and spoken, is essential. 

Eligibility criteria  

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

1. You must not already hold a doctoral degree.
2. 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 Switzerland for more than 12 months in the three years prior to the contract start date.
3. You must be able and willing to work in an international training network, participate in network-wide training activities and undertake planned secondments with POLARIS partner organisations.