About the Project
Melanin is a pigment in animal skins and cuticles. Naturally occurred mutations in genes in melanin synthesis pathways cause condition called albinism across animal kingdom. We and others recently found that gene orthologues of oca2 and slc45a2, the two melanin synthesis genes, express in the nervous system. The mutations of these genes cause sleep and vision phenotype in the fruit fly Drosophila and cavefish (1, 2). Sleep is required for regulating neural activity. Evidence indicates that vision and sleep regulate each other (3-5). Our finding therefore suggests an evolutionary conserved function of pigmentation genes in nervous system. This PhD project, therefore, aims to use the highly genetically editable model, Drosophila, to uncover this novel sleep controlling mechanism by the following objectives.
- Neural circuits: using scRNA-seq data (1), the student will identify cells enriched with oca2 and slc45a2 in the fly brain. Vertebrate and fly oca2 and slc45a2 transgenes will be reintroduced into these cells and verify if sleep and visual phenotype in oca2 and slc45a2 mutants is reversed. Connectome (6) will then be used to define neural connection between oca2/slc45a2-expressing neurons and the sleep controlling circuits.
- Neuronal function: oca2 and slc45a2 are predicted to control sleep-related neurotransmission by regulating neuronal pH and Cl- (1). Using fluorescence reporter in brain imaging, the student will verify whether oca2/slc45a2 mutations cause altered pH and Cl- levels.
- Sleep and vision interaction: to verify if sleep modifies the visual defect in oca2/slc45a2 mutants, the student will perform electroretinogram before and after artificially enhancing the mutants' sleep by drug feeding or optogenetically activating sleep promoting circuits.
Techniques that will be undertaken during the project
The student will be trained by the primary supervisor for the following techniques Drosophila genetics, sleep assay, in silico brain imaging, ex vivo confocal brain imaging, and electroretinogram for assessing visual phenotype. The secondary supervisors will provide training for general bioinformatics analysis. Specifically, the project will also be supported by two collaborators Dr Clifton Lewis on scRNA-Seq and Dr Nils Reinhart on brain connectomics.
Enquiries
Project Enquiries to [contact details available in the full listing]
Programme enquiries to [contact details available in the full listing]
To apply please refer to https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
Funding Notes
All MIBTP students will be provided with a 4 year studentship. This includes: Tuition fees at the UK fee rate*, a tax free stipend which for 2026/7 is £21,805 per year (2027/8 stipend to be confirmed), a travel allowance over years 1-3, a travel/conference budget, a generous consumables budget, use of a laptop for the duration of the programme. The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.
References
(please use ID provided to locate references on https://europepmc.org/)
- PPR: PPR1243431.
- PMID: 34293332.
- PMID: 31100151.
- PMID: 30355611.
- PMID: 41815955.
- PMID: 39638801
