Māori health research PhD scholarship (2018 funding round)

Miss Blaise Forrester-Gauntlett
University of Auckland
Using pluripotent stem cells to determine the cellular basis of hearing loss
$79,303
36 months

Lay summary

The aim of this PhD research proposal is to elucidate the function of the Grainyhead-like 2 gene (Grhl2), which is genetically associated with auditory sensory hair cell formation and age-related hearing loss (ARHL).

We will use genome editing to generate two different loss-of-function Grhl2 mutations in mouse embryonic stem cells (ESCs). This includes 1) a gene-matched point mutation that mimics the genotype found in humans with Grhl2-dependant ARHL and 2) a large deletion that completely disrupts Grhl2. Heterozygous and homozygous mutant ESC lines will be molecularly and functionally evaluated using three-dimensional in vitro differentiation into inner ear-like organoids and tetraploid embryo complementation to generate an in vivo mouse model.

Our study will help to understand the cellular basis of Grhl2-dependant ARHL. This may lead to the identification of therapeutic targets for intervention, treatment or prevention of ARHL, which disproportionally affects New Zealand Māori.

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