Harmansa Group

Project summary – This PhD project will explore how BM growth and structure generate stresses that mechanically guide early vertebrate eye morphogenesis. During eye development, the optic vesicle epithelium bends inward to form the optic cup. This bending depends critically on the BM: Mutations in BM components cause severe defects in optic cup formation in zebrafish and chicken embryos. Interestingly, optic cup invagination is rapid and linked to cell migration in zebrafish, but slower and likely migration-independent in chickens. These species-specific differences highlight an essential yet unresolved role for the BM in shaping the developing eye.
Building on recent findings of our group showing that BM growth can drive stress accumulation, elastic deformation and tissue bending, this project will test whether species-specific differences in BM growth and remodelling explain the contrasting dynamics of optic cup morphogenesis.
This PhD offers unique training at the interface of developmental biology, biophysics and computational modelling, as well as cross species analysis in zebrafish and chicken embryos. The successful candidate will employ developmental genetics (transgenesis in zebrafish), high-resolution live imaging and quantitative biophysical methods (AFM, laser ablation) with genetic perturbations, while collaborating with theorists to integrate experimental data into computational models. This interdisciplinary project offers training at the interface of developmental biology, biophysics, and computational modelling, as well as cross-species analysis in zebrafish and chicken embryos. The successful candidate will gain expertise in cutting-edge microscopy, quantitative data analysis, and biophysical methods, and will join a collaborative, international research environment.

Get in touch with Stefan for more details or to informally discuss the project (s.harmansa@ exeter.ac.uk).

Project summary – How do tissues bend, fold and sculpt themselves into functional organs? This central question in developmental biology lies at the heart of morphogenesis, where mechanical forces and extracellular structures work together to shape tissues. The basement membrane (BM) is a specialised extracellular matrix that not only supports epithelia but also actively drives their form. Its major structural component, Collagen IV, builds a crosslinked network essential for stability, growth and signalling. Mutations in Collagen IV compromise BM integrity, leading to developmental defects and human diseases, including eye malformations, kidney disorders and vascular pathologies. Despite this broad relevance, the mechanical role of the BM in shaping organs is still poorly understood.

This PhD project will investigate how Collagen IV organisation and BM dynamics generate mechanical stress and drive morphogenesis across species. Two powerful in vivo models, the Drosophila wing disc and the zebrafish optic cup, provide complementary systems in which epithelial sheets bend into dome-like shapes. Both processes critically rely on BM mechanics, yet the underlying principles remain unclear. Building on our recent discovery that BM growth drives stress accumulation and tissue bending in the fly wing (Harmansa et al., Nat. Commun., 2024), we will test whether similar mechanisms govern vertebrate eye development.

The candidate will combine cutting-edge genetics (CRISPR-Cas9), advanced live and super-resolution imaging, and biophysical techniques (atomic force microscopy, laser ablation, rheology) with theoretical modelling. This interdisciplinary approach will reveal conserved principles of BM-mediated morphogenesis, offering insights with broad
impact on collagen-related diseases and future applications in tissue engineering.

Get in touch with Stefan for more details or to informally discuss the project (s.harmansa@ exeter.ac.uk).