Development of an Embryonic Chick Model for In Vivo Study of Human Congenital Cataracts (360G-Wellcome-341890_Z_25_Z)

Congenital cataracts are the leading cause of childhood blindness, resulting from disorganisation of lens fibres and protein accumulation that disrupts lens transparency. The mechanistic basis for most genetic variants remains unclear. My project aims to use a chick embryo model to understand how mutations affect lens formation and function. My project has two aims: 1\. To test if pathogenic human genetic variants cause congenital cataract when introduced into the chicken lens. I will perform microinjection of mutated gene constructs into the embryo to determine if their expression results in abnormal lens structure and refractive properties. In parallel, I will generate a stable gene-edited chicken line with an allele associated with early-onset human cataracts. 2\. To identify the changes in gene expression, protein abundance and activities, and the metabolic effects that occur when cataracts develop using the chicken embryo model system. This could reveal common pathways and targets that could be used to explore new diagnostic and treatment strategies. The combination of both genetic approaches will allow in-depth characterisation and comparisons of the effects of the introduced mutations using a biomedically-relevant, reproducible and scalable model system. The outcome of this work could lead to improved non-surgical treatments for children with cataracts.