MSCA-DN PhD in preclinical outcomes in zebrafish models of leukodystrophies

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.

PhD project

For this position, the recruiting organisation is the University of York, UK. The selected candidate will be employed by the University of York and become part of the POLARIS consortium, with academic supervision and disease-specific expertise provided by Dr Noémie Hamilton at the York Biomedical Research Institute and the Department of Biology at the University of York.

You will focus on developing and standardising robust preclinical outcome measures across multiple zebrafish models of leukodystrophy, including models of RNASET2 deficiency, adrenoleukodystrophy (ALD), Krabbe disease and metachromatic leukodystrophy (MLD).

Zebrafish are widely used to model leukodystrophies because of their genetic tractability and the ability to study early brain development. To strengthen their use as preclinical models, this project will develop outcome measures that are robust, reproducible and relevant to assessments used in patients and mammalian disease models.

Your research will combine different approaches to:

• Develop and standardise behavioural assays across multiple zebrafish models of leukodystrophy.
• Characterise disease phenotypes using multimodal imaging and complementary experimental approaches.
• Apply advanced imaging techniques, including MRI, high-resolution confocal microscopy and electron microscopy.
• Develop and refine imaging analysis pipelines, using appropriate software, quantitative approaches and innovative analytical methods.
• Compare and benchmark preclinical outcomes across different disease models and against clinically relevant measures.
• Identify robust and reproducible readouts that can support the use of zebrafish in preclinical therapy development.
• Work collaboratively across different research environments, integrating findings from zebrafish models with data from mammalian models and other experimental systems.

As part of the POLARIS training programme, you will undertake planned secondments that complement your research at the University of York.

At Zantiks, you will gain hands-on experience with behavioural analysis equipment and software and learn how ideas emerging from academic research can be developed towards commercial application.

You will also undertake a secondment at the University of Liverpool’s Centre for Preclinical Imaging, a leading preclinical imaging centre with access to advanced technologies including MRI, PET, CT, SPECT, ultrasound, photoacoustic imaging, magnetic particle imaging (MPI), optical imaging and hyperthermia. These technologies can be applied across a range of experimental models, including cells, organoids, Drosophila, zebrafish and rodents.

The academic research and PhD defence will be based at the Department of Biology at the University of York.

We are looking for a motivated candidate with a strong interest in translational neuroscience, rare disease research and the development of robust preclinical models. You bring:

• A Master’s degree in life sciences or a related field.
• Experience with microscopy and image-data analysis, ideally gained through research projects or internships involving in vivo zebrafish models.
• Experience with behavioural or neurological phenotyping is advantageous.
• Experience with animal research, animal-welfare principles and robust experimental design is advantageous.
• An interest in developing imaging analysis pipelines using innovative or novel approaches.
• Experience with coding, specific imaging software such as GA3 Elements, machine learning or quantitative image analysis is advantageous.
• A strong interest in understanding how preclinical readouts can be aligned with clinically meaningful endpoints.
• A willingness to work with researchers using different disease models and to use these models to benchmark and develop your assays.
• A curious and critical mindset, with the ability to evaluate experimental approaches and interpret complex datasets.
• An accurate and reproducible approach to research, with strong attention to detail and the ability to plan and organise complex experimental work.
• Good communication and collaboration skills, with the ability to work across different research environments and disciplines.
• The ability and willingness to work in an international and interdisciplinary research environment, collaborating with colleagues at the University of York and across the POLARIS consortium.

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

As part of your appointment, you will complete the required UK Home Office training and certification to work with animals in accordance with UK regulations.

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 the UK 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.