MRes - Developing treatments for Batten disease, a childhood neurodegenerative disease
Lead RVC Supervisor: Dr Claire Russell, Dr Valentina Marchica
Department: Comparative Biomedical Sciences
Background, aims and objectives:
The zebrafish is a prominent model to study inherited diseases. Mutations in CLN3 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 juvenile CLN3 disease (~45 currently in the UK, estimated >700 new cases diagnosed annually world-wide) suffer from rapid visual failure from 5 yrs3, followed by seizures and a progressive cognitive and psychomotor decline, with death by the fourth decade. 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 antisense morpholino models (morphants) of CLN3 disease4 and have data showing varying efficacy of several compounds for treating our zebrafish morphant model of CLN3 disease. The most effective treatment has side-effects, so we wonder if we could reduce the amount of it (and therefore its side-effects) by combining it with one of the other compounds.
References
- Mole SE, et al., eds. The neuronal ceroid lipofusinoses (Batten disease). 2nd ed. Contemporary Neurology 2011, Oxford University Press: Oxford. 444.
- Warrier V, et al., Biochim Biophys Acta, 2013.
- Wright GA, et al., Ophthalmol Retina, 2020.
- Wager K, et al., PLoS One, 2016. 11: e0157365.
Requirements
Essential:
- Must meet our standard MRes entry requirements.
- No need to be a vet, willingness to work with zebrafish animal model (embryos up to 5 days post-fertilisation), strong motivation and commitment to learning.
Desirable:
- Previous lab experience. Experience using zebrafish.
Fees and Funding
This can be taken full-time or part-time (12months FTE) project commencing in October 2025, based at RVC's Camden campus.
The animal model used is the zebrafish embryo (up to 5 days post-fertilisation), therefore no É«ÇéÖ±²¥app Office personal licence is required for this project. Any regulated procedures would be performed by the supervisors. However, there may be the opportunity to acquire a É«ÇéÖ±²¥app Office Personal License.
Partially funded: The lab will be covering the project costs, with the MRes student expected to meet the course fees and their living expenses.
International applicants are welcome to apply but must be able to fund the difference between "É«ÇéÖ±²¥app" and "Overseas" tuition fees.
Please note that EU/EEA and Swiss national students may no longer be eligible for the “É«ÇéÖ±²¥app” 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 p²¹²µ±ð.
How to Apply
For more information on the application process and English Language requirements see How to Apply.
Deadline: 04/04/2025
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