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
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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