Understanding the impact of alternative splicing of ciliary genes on the development and maturation of human photoreceptors


 

Marina Moya Molina (ESR 4)

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Marina was born in Granada, Spain and obtained her Bachelor’s degree in Biochemistry at the University of Granada. During her degree, she participated in an Erasmus+ Exchange programme at the University of Durham, UK. Marina continued her studies and did a Master’s Degree in Health Biotechnology at the University of Pablo de Olavide, Sevilla. Her Master’s Thesis was focused on stem cell and gene therapy in retinal diseases, where she worked with iPSCs and CRISPR/Cas9 technique. During this time, she gained lot of interest in retinal diseases leading her to apply for another Erasmus+ Exchange programme in the Retinal Stem Cell Research Group of Newcastle University. After her rewarding internship, she applied for a phD as part of the SCilS programme, where she will investigate the impact of alternative splicing of ciliary genes on the development and maturation of human photoreceptors.

Abstract
Alternative splicing is a pre-mRNA processing step regulating the selection of specific exons/introns to produce different transcripts from one genomic locus. Retinal tissue has one of the highest levels of alternative splicing, and mutations in splicing factors and dysregulation of splicing is associated with retinal disease. A recent study in mouse has shown that retinal development is characterised by dynamic changes in splicing, with differential splicing events occurring more frequently during early development. In particular the photoreceptors are characterised by a specific splicing program that displays a switch like pattern with high exon inclusion levels in photoreceptors and almost complete exclusion outside the retina. Previous studies have shown that PROM1 displays increased exon 4 inclusion (54%) and exon 24 skipping (44.4%) during 12th-18th week of human development, a developmental window characterised by photoreceptor differentiation and maturation. The aim of this project is to investigate the dynamics of PROM1 alternatively spliced isoforms generation and their impact on photoreceptor differentiation and maturation. Retinal organoids generated from human pluripotent stem cells and morpholinos, which block PROM1 alternative splicing, will be used to achieve this goal.