Supervisor: Dr Anne Lagendijk (a.lagendijk@imb.uq.edu.au)
A healthy vasculature is central to a functioning cardiovascular system. One aspect imperative to a homeostatic vascular system is the integrity of junctions between adjacent endothelial cells (ECs). It is appreciated that arteries and veins display different adhesive properties at EC junctions, underpinning their distinct functions. However, the molecular mechanisms controlling this heterogeneous adhesion and junction integrity across divergent vessel types are not well understood.
Preliminary data in our lab has uncovered a novel factor that specifically controls venous EC adhesion. We have shown this specific role in both loss-of-function zebrafish and 3D bioengineered human vessels, displaying disrupted venous endothelial junctions and venous vessel dysmorphia. Notably, arteries are unaffected. Such vessel-restricted phenotypes are rare, and this project aims to characterise the cellular mechanisms that determine this specificity. We are seeking an enthusiastic and driven Honours student to assist in the phenotyping of novel zebrafish CRISPR knockout lines that have been generated as part of this project. You will gain skills in zebrafish handling, molecular cloning, CRISPR/Cas9 gene editing and high-resolution live imaging of functioning blood vessels. Specific project aims include:
1. Phenotypic rescue experiments by re-expressing genes in zebrafish knockout models
2. Determine the functional consequences of compromised ECs (i.e. vessel hyperpermeability or breakdown) using dextran injections
3. Assist in phenotyping of novel CRISPR/Cas9 zebrafish mutant lines to help delineate the key players in this novel venous specific pathway
