Supervisors: Dr Claire Russell and Imelda McGonnell

Department: Comparative Biomedical Sciences

Project Details:

The zebrafish is a prominent model to study inherited diseases. Mutations in the Tri-Peptidyl Peptidase 1 gene cause approximately half the cases of a group of severe recessively inherited neurodegenerative disorders affecting children1, the neuronal ceroid lipofuscinoses (NCL) or Batten disease. These are life-limiting monogenic recessive disorders that affect lysosomal homeostasis, with increased accumulation of autofluorescent lipofuscin2. Those affected by classic late infantile CLN2 disease (35-50 currently, estimated 3-6 new cases diagnosed annually, in the UK) suffer from the age of about 2 years old from seizures, vision loss and a progressive cognitive and psychomotor decline, with death by the age of 13. A treatment (Brineura) exists but in the UK, NICE have not approved it for new patients due to the cost. Hence other treatments are needed. Neurodegenerative diseases affecting children and young adults represent a significant unmet clinical need and are a health and socioeconomic burden for families and society. 

We have published a zebrafish mutant model of CLN2 disease2 which recapitulates many features of the disease. We have data suggesting that iron accumulation occurs (as seen in patients)3,4, and that the iron accumulation decreases with disease severity. In this project, we will test if iron chelation, a treatment already available for other diseases, improves the phenotype of the zebrafish mutant model of CLN2 disease2 . 

References:

1. Mole SE, et al., eds. The neuronal ceroid lipofusinoses (Batten disease). 2nd ed. Contemporary Neurology 2011, Oxford University Press: Oxford. 444.
2. Mahmood F, et al., Dis Model Mech, 2013. 6: 652-60.
3. Grubman et al., Metallomics, 2014, 6: 932-943.
4. Gutteridge et al., Acta Neurologica Scandinavica, 1983, 68:365-370.

Requirements

Essential:

• Must meet our standard MRes entry requirements. (No need to be a vet).
• Strong motivation and commitment to learning.
• Willingness to work with the zebrafish animal model, to become trained and competent in zebrafish euthanasia, and to perform euthanasia when required.

Desirable:

• Previous lab experience. 
• Experience using zebrafish

This can be taken full-time or part-time (12 months FTE) project commencing in October 2026, based at RVC's Camden campus.

The animal model used for experiments is the zebrafish embryo (up to 5 days post-fertilisation), therefore no Home Office Personal License is required for the experiments performed in this project. However, the genetically-altered adult zebrafish used to generate the embryos are covered by Home Office Licensing. Any regulated procedures on fish older than 5 days post-fertilisation would be performed by the supervisors under their Personal License and the existing Project License. As breeding and Schedule 1 euthanasia are not procedures, the student can breed the adults and euthanise fish of any age without a Personal License.  There may be the opportunity for the student to acquire a Home Office Personal License, if they wish.

Funding:

Fully Self-funded: The MRes student will be expected to meet some of the project costs (£3000 for zebrafish husbandry maintenance), their course fees and their living expenses. The supervisors will meet the costs of other consumables (plastics, gloves etc). If the student wishes to train for a Home Office personal licence (optional), the student is expected to pay those costs (£435 + VAT).  

Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page.

Deadline: 8th May 2026

For more information on the application process and English Language requirements see How to Apply

Interviews will take place remotely (Teams, Zoom etc) within 4 weeks of the closing date. We welcome informal enquiries - these should be directed to crussell@rvc.ac.uk