Current Research Interests
Patterning, Regeneration & Evolution of Cone Photoreceptors
The zebrafish cone photoreceptor types, very similar to those of the human fovea, are shown in long section below. The green label (GFP) is in UV-sensitive cones. The blue/red coloured cells above the UV cones are red-sensitive and green-sensitive cones.
The pattern of the cones in cross section across the eye is shown below - the cones are positioned evenly across the back of the eye, as shown in the bottom left. The four cone types are positioned with great precision relative to one another, as shown in the bottom right. I am interested in how these cones differentiate and how they are able to take on precise positions relative to one another; perhaps the mechanisms are similar to the ones that position the ommatidia in the fly eye. I am also interested in what adaptive value this precise array of cells might have - maybe it helps the fish's spatial vision or its ability to discriminate polarized light.
Another interest I have is centered on the ability of these photoreceptors to regenerate from retinal stem cells. This provides important opportunities to study what genes are required to turn stem cells into cones; this is a major goal in strategies to repair human blindness in retinal degenerative disease. I am also developing zebrafish as models of neurodegenerative disease, especially Prion Diseases (Mad Cow, Chronic Wasting Disease in deer) and Alzheimer Disease. This work is being completed in the Centre for Prions & Protein Folding Diseases
. The zebrafish is emerging as a powerful international resource for researchers investigating how cells of the nervous system develop, degenerate, and are repaired. Zebrafish combine the advantages of many experimental systems: they grow quickly and can be maintained inexpensively in very large numbers; they grow external to the mother, and thus gene expression and drug treatment effects can be monitored outside of a placenta; zebrafish have brain architectures and genes that are strong approximations of those in humans, and the genome has been sequenced. Importantly, the genes of zebrafish can be readily manipulated within individual cell types, allowing us to establish zebrafish as a powerful tool in Prion and Protein Folding Disease research.
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