Miss Alexia A. Kalligeraki, BSc (Hons) Biomedical Science (Immunology)
(email at email@example.com)
Protein stability is essential to the physiological function of cells, and this is mostly achieved by the stabilisation and turnover of damaged macromolecules. The bulk of the eye lens consists of organelle-free, transparent fiber cells which do not have the capacity to synthesise new macromolecules, and as such the accumulated proteins and lipids are retained throughout the lifespand of the organism. As a result, the macromolecules in the lens core are retained over decades and are subject to a lifetime of modifications and damage, including oxidative stress. The aggregation of damaged proteins eventually leads to the formation of cataract, which is the leading cause of blindness worldwide.
The lens utilises a high concentration of the chaperone protein α-crystallin and cholesterol-rich membrane bilayers to stabilise misfolded and damaged proteins and to maintain the hypoxic environment required for lifelong tissue transparency. The age-related decline in crystallin chaperone activity, in combination with the enrichment of the lens lipidome with cholesterol lead to the eventual formation of macromolecule aggregates which are susceptible to further oxidative insults and accelerate the formation of light-scattering adducts in cataract.
My doctoral research focuses on the interplay between the lens proteome and the lens lipidome in the context of α-crystallin activity and the role of supplemental sterols in regulating its chaperone action. I have used in vivo pharmachological models to characterise the effect of cholesterol synthesis inhibition on the developing zebrafish and whether sterol supplementation can restore associated vision defects. I have also analysed the influence of oxysterol supplementation on the chaperone activtiy of α-crystallin in the context of healthy and cataract-derived lens lysates in vitro.
My main research interest involves the role of chaperone proteins in protein-aggregation diseases, such as cataract, and how the cellular environment contributes to the escalation of proteinopathic phenotypes.
Simultaneously, I am interested in the geometric characterisation of lens epithelial cell distribution using advanced light microscopy techniques and computational modelling to understand how their organisation influences lens shape and lens fate. As lens epithelial cell distribution is subject to both age-related and environmental-mediated (ie., ionising radiation) changes, it is crucial to understand the relationship between an appropriate cell population and physiological tissue function.
- Alexia A Kalligeraki, Archie Isted, Robert Pal, Chris Saunter, John Girkin, Miguel Jarrin, Alice Uwineza, Boguslaw Obara & Roy A Quinlan (2020). Three-dimensional data capture and analysis of intact eye lenses evidences emmetropia-associated changes and strain-dependent differences in epithelial cell organization. Scientific Reports 10: 16898.
- Uwineza, Alice, Kalligeraki, Alexia A., Hamada, Nobuyuki, Jarrin, Miguel & Quinlan, Roy A. (2019). Cataractogenic load – a concept to study the contribution of ionizing radiation to accelerated aging in the eye lens. Mutation Research/Reviews in Mutation Research 779: 68-81.