Decomposing optic cup formation using a morpho-elastic computational model

Supervisors:

• Jochen Kursawe (University of St Andrews)
• Joe Rainger (University of Edinburgh)

The visual function of the eye is dependent on early eye morphogenesis and cell proliferation to acquire the necessary 3-dimensional shape and size of a mature eye. Alterations in eye development and morphogenesis lead to the developmental eye disorders Microphthalmia (reduced eye size), Anophthalmia (no eye) and Coloboma (morphological defects) which occur in 1 in 10000 births and account for up to 25% of childhood blindness. The 3D shape of the eye or optic cup must be generated through invagination and subsequent merging (fissure closure) of a sheet of cells in a complex process called optic cup morphogenesis.

Several cell behaviours have been hypothesised to be the key driving forces of optic cup morphogenesis including cell shape changes driven by pulsatile constrictions on the basal side of the cell, movement of cells at the rim of the optic cup to the inner layer, differential tension across the tissue and differential growth and spatial constriction leading to tissue buckling. However, the relative contribution of each process is currently unclear and how these processes go awry in developmental disorders is unknown. Dissecting this in the lab is challenging as optic cup morphogenesis is complex and the underlying processes likely feedback on each other and share similar molecular components.

During this PhD we aim to model optic cup morphogenesis to dissect this complex interplay of forces and processes. The student will generate a computational model of optic cup morphogenesis using a finite-element morpho-elastic model. Importantly, the model will consider invagination of the optic cup as well as closure of the optic fissure. The model will be informed by and validated against published quantitative characterisations of cell number, cup geometry, and cell signalling over time. This will allow us to test the relative importance of cell shape changes, cell movement, differential tension and spatial constraints and allow us to make predictions about which processes have the greatest influence on optic cup morphogenesis. Our results will be used to inform experimental approaches by our collaborators at the Universities of Edinburgh and Manchester to test our hypotheses in the developing zebrafish and chick eye. Overall, the project will advance knowledge of how eyes develop and help us to understand the processes that contribute to developmental eye disorders.

HOW TO APPLY

Application instructions can be found on the EASTBIO website- https://biology.ed.ac.uk/eastbio/how-to-apply

1. Download and complete the Equality, Diversity and Inclusion survey.
2. Download and complete the EASTBIO Application Form.
3. Submit an application to St Andrews University through the Online Application Portal

Your online application must include the following documents:

• Completed EASTBIO application form
• 2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)
• Academic Qualifications
• English Language Qualification (if applicable)

Unfortunately, due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by 17^th January 2025

CONTACT

Queries on the project can be directed to the project supervisor (Jochen.kursawe@st-andrews.ac.uk)