Understanding The Role Of Circular RNAs In Neuronal Biology Using RNA-targeting CRISPR/Cas9
Funder
National Health and Medical Research Council
Funding Amount
$398,097.00
Summary
The regulation of gene expression through a process known as RNA splicing has been shown to be at the heart of a number of processes required for brain development, memory and learning, and is often dysregulated in a number of neurological diseases. Circular RNAs (circRNAs) have been recently shown to be a relatively abundant class of spliced RNA that are specifically enriched in brain tissue. In this project, I aim to understand the roles of circRNAs in neuronal development.
Structural Characterisation Of Long Non-Coding RNA Bound Histone Modification Complexes
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is a disease associated with genetic and epigenetic changes of DNA. Epigenetics involves external changes to the DNA, switching processes “on” and “off”, to regulate gene expression. This project aims to provide powerful insight into key processes involved in epigenetic-based carcinogenesis, and thereby lay the foundation for producing novel cancer diagnostic markers and molecular based therapies.
Design Of Cas9 Nucleases With Reduced Basal DNA Binding And Enhanced Recombinase Activity For Human Genome Engineering
Funder
National Health and Medical Research Council
Funding Amount
$385,761.00
Summary
Cas9 has recently emerged as a transformative tool for genome engineering. The enzyme is guided by a short RNA to pair with a DNA sequence of interest and to introduce a break. This DNA break becomes a substrate for repair pathways: Non-Homologous End-Joining or Homologous Recombination. The rate of HR is typically lower, limiting the efficiency of insertion of new DNA. The project aims to determine these reasons for limited rates of HR, and to improve these rates through protein engineering.
Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Investigating Mechanisms Of Dementia And Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$303,924.00
Summary
Dementia and motor neuron disease (MND) are both neurodegenerative diseases which have devastating impacts on patients and their families. My research investigates the biochemical mechanisms involved in these diseases. Pathology in the nervous system of dementia and MND patients contains a protein called ‘TDP-43’, but it remains unknown how this causes disease. This project will therefore explore the effects of TDP-43 malfunction, which will provide insight into potential therapeutic strategies.