Our research programme is focused on understanding the molecular processes that are required for formation and storage of memory, and how their disruption can lead to neurological disease. In recent years it has become clear that abnormal accumulation of the histone deacetylase HDAC4 in neuronal nuclei is associated with both neurodevelopmental and neurodegenerative disorders, and in our *Drosophila* model, increased nuclear HDAC4 also impairs neuronal development and memory. When increased in abundance in nuclei, HDAC4 forms into aggregates, which is mediated through an N-terminal *a*-helix. We have determined that mutation of amino acids predicted to prevent tetramerisation both prevents aggregate formation and reverses any developmental deficits. These preliminary data strongly suggest that the aggregates are responsible for the impairments, but it is not clear what causes these aggregates to form, their composition and what it is that makes them pathogenic.
This project seeks to answer these questions. Approaches include determining the impact of specific mutations on the formation of the N-terminal *a*-helix and tetramer of recombinant HDAC4 protein via a variety of biochemical techniques under the guidance of co-supervisor Assoc Prof Andrew Sutherland-Smith. It will also include testing strategies to ameliorate aggregation-induced impairments in *Drosophila* models of neurodegeneration.
PhD Scholarships, New Zealand 2022-23 is available to undertake PhD level programs at Massey University.
Following subject are available to study under this scholarship program.
Massey University will provide an award amount of $105,000 plus tuition fees for three years only for successful candidates for a PhD degree.
Applicants should have a relevant postgraduate degree relevant to the above-described research areas and be highly motivated and able to work as part of a team. Experience in molecular biology is required and a background in neuroscience and/or Drosophila genetics would be an advantage. Due to the current border restrictions, this opportunity is currently only available to applicants already in New Zealand.