I’m pleased to announce that we are now accepting applications for a PhD studentship between my lab at the University of Liverpool and Professor Roy Quinlan at the University of Durham. The official advert will be online soon, however if you know of anyone who is interested, please let them know and have them get in contact with myself or Roy.
Determination of laminin LN domain roles in tissue function, using Pierson syndrome and the lens capsule as a model.
Laminins are a major structural component of all basement membranes. Each laminin is a heterotrimer capable of interacting with cell surface receptors (integrins, dystroglycan, syndecan) and other matrix proteins including nidogens and perlecan. Additionally, laminins assemble into networks, a feature controlled by sequences within their (laminin) LN domains. Missense mutations in this domain are pathogenic and when they occur in LAMB2 they lead to Pierson Syndrome.
The aim of this studentship is to determine the mechanisms through which LN domain mutations impact tissue function. Our focus will be Pierson syndrome (https://rarediseases.info.nih.gov/diseases/9420/pierson-syndrome), where patients present with lens abnormalities including abnormal shape and cataract formation. The lens capsule is a specialised BM that is one of the thickest human BMs, it that can be readily isolated and support the in vitro culture of cells. Moreover, the lens capsule contains a limited subset of laminins making it a tractable system for asking the focused questions proposed here.
Using CRISPR-Cas9 genome editing technology, Pierson syndrome mutations will be introduced into human lens epithelial cells (FHL124). We will then combine these cells, with isolated bovine lens capsules that have been treated to remove existing LMs to generate 3D physiologically relevant systems in which all three of the potential BM functions can be assessed (mechanical/signalling/growth factors binding)
This studentship will also test the hypothesis that pathogenic mutations will influence the BM function in a context specific manner.
Primary Supervisor: Dr Kevin Hamill:https://www.liverpool.ac.uk/ageing-and-chronic-disease/staff/kevin-hamill/
Durham Supervisor: Prof Roy Quinlan: https://www.dur.ac.uk/biosciences/about/schoolstaff/profile/?id=36