PhD studentship opportunity at City St George’s University of London

Title of project: Functional characterisation of FRIZZLED5 variants associated with coloboma and microphthalmia

Supervisory Team –

Dr Florencia Cavodeassi – fcavodea@sgul.ac.uk

Dr Alan Pittman – apittman@sgul.ac.uk

Dr Christopher Carroll – ccarroll@sgul.ac.uk

Location: City St George’s University of London

Closing date: Sunday 26 January 2025, 23.59 GMT

Starting date: 1^st October 2025

Application details: https://www.sgul.ac.uk/study/postgraduate-study/research-degrees/phd-programme

We are looking for an enthusiastic candidate to join us from the 1^st October 2025 on a PhD project entitled “Functional characterisation of FRIZZLED5 variants associated with coloboma and microphthalmia”. The successful candidate will join our vibrant community of PhD students at City St George’s University of London and will gain training in a range of molecular, cell and developmental biology approaches while studying the molecular mechanisms involved in ocular malformations.

Project details

Ocular coloboma and microphthalmia are congenital structural malformations of the eyes caused by defective eye morphogenesis during early embryonic stages. These malformations can occur in isolation, in combination, or as part of a broader syndrome, exhibiting considerable genetic heterogeneity. Recent studies have uncovered 21 mutations in the Wnt receptor FZD5 associated with microphthalmia and/or coloboma in humans. Variants are found in all domains of the protein, and there is no clear association between ocular phenotypes and type of mutation.

Only two of the 21 FZD5 variants have been functionally analysed in vitro and in vivo, limiting our understanding of the mechanisms by which those variants lead to the diverse phenotypic outcomes found in patients. This lack of understanding also impacts negatively in our ability to predict the effect of novel mutations in FZD5 or provide genetic counselling.

The aim of this project is to determine the association of selected FZD5 mutant variants to specific phenotypes, by categorising and functionally analysing them.

Skills

The student will be trained in a wide range of experimental approaches. in vitro and in vivo functional approaches (including embryology, molecular biology, biochemical and cell biology approaches) will be exploited to determine levels of activity of the variants under analysis in cells in culture and zebrafish embryos. This training will provide the student competence in diverse approaches in Biomedical Sciences and awareness of state of the art approaches for functional analysis of human disease genetic variants.

The student will be trained in robust computational analysis for in silico modelling of the variants under analysis. They will also search databases such as the 100K Genome Project and GeneMatcher, to identify further individuals with potentially pathogenic variants in our gene of interest.