Stabilising the Corneal Stem Cell Niche: LaNt α31 as a Regulator of Epithelial Repair and Regeneration

About the Project

Discover how a little‑known laminin‑related protein, LaNt α31, shapes the human limbal stem cell niche. Using stem‑cell models, advanced imaging and engineered tissues, this project investigates how the basement membrane controls epithelial identity and explores new therapeutic strategies for corneal repair and regenerative medicine.

The front of the eye is constantly exposed to the external environment, yet maintains a clear, stable, and self‑renewing surface throughout life. This remarkable resilience depends on limbal epithelial stem cells (LESCs), which reside in a specialised niche at the corneal periphery. Their ability to remain quiescent, activate for repair, or differentiate into corneal cells is tightly controlled by cues from the extracellular matrix. When this regulation fails, such as in injury, chronic disease, ageing, or stem‑cell deficiency, patients can develop painful erosions, scarring, and vision loss. Understanding how stem‑cell behaviour is instructed by matrix signals is therefore a critical step towards developing new regenerative therapies for the ocular surface.

Recent data from our lab point to a previously overlooked but powerful regulator of the limbal niche: LaNt α31, an alternatively spliced laminin‑derived protein. Our data has shown that LaNt α31 has surprisingly broad effects, it remodels laminin‑332 networks, alters adhesion structures, and shifts epithelial cells towards a more progenitor‑like identity. These findings suggest that LaNt α31 may function as a stem cell “niche stabiliser”, helping to hold stem‑cell‑like cells in place, reinforce their basal identity, and prevent premature differentiation. Yet the mechanisms behind this behaviour remain unknown. This is where your PhD project begins.

In this project, you will investigate how LaNt α31 controls stem‑cell state, basement‑membrane architecture, and epithelial behaviour. Working with human limbal epithelial cells, advanced 3D corneal models, and state‑of‑the‑art super‑resolution imaging, you will map how LaNt α31 coordinates laminin processing, syndecan signalling, and ECM organisation to create a microenvironment that supports stem‑cell maintenance.

Your work will address three key questions:

1. How does LaNt α31 reshape laminin‑332 architecture in the limbal niche? You will use high‑resolution and super‑resolution microscopy to visualise basement‑membrane organisation at nanoscale resolution and determine how LaNt α31 modifies ECM patterning and adhesion structures.
2. How does LaNt α31 influence stem‑cell identity and differentiation cues? We will analyse gene‑expression changes, differentiation markers, and secreted factors to uncover how LaNt α31 drives cells towards a basal, progenitor‑like state and suppresses migration‑associated or repair‑associated pathways.
3. Can LaNt α31‑dependent mechanisms be harnessed to improve corneal repair? Using biomimetic 3D limbal and corneal tissue constructs, you will test how LaNt α31 affects stratification, hemidesmosome formation, barrier integrity, and wound‑closure dynamics. These experiments provide a translational link, offering a path toward developing ECM‑based therapies or conditioning strategies that stabilise the niche in disease or after injury.

By the end of the PhD, you will have developed a unique mechanistic understanding of how the limbal niche is stabilised, contributed new insights into stem‑cell regulation, and created tools or models with clear potential for future therapeutic development.

This project is ideal for students excited by stem‑cell biology, matrix biology, regenerative medicine, and advanced imaging. You will receive training in cell and molecular biology, genome editing, quantitative imaging, ECM analysis, organotypic culture, and corneal biology, supported by a collaborative supervisory team with expertise in laminins, niche biology, and 3D tissue engineering.