Systematic And Sensitized Screens For Novel Genes That Regulate The Neural Differentiation Of Mouse Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$360,634.00
Summary
Embryonic stem (ES) cells are cells in the embryo that can transform into any cell type. Genes that direct mouse ES cells to transform into cells of the nervous system will be uncovered by selecting a group of likely suspects, and disrupting the DNA sequences of these genes to see whether neural differentiation occurs normally in their absence. The effects of the gene disruptions will be examined in the developing neural system of the mouse embryo.
Identifying Rare Genetic Variants Conferring Susceptibility To Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$293,898.00
Summary
Recently there has been success in identifying common genetic variants that confer susceptibility to multiple sclerosis. The variants that have been discovered so far have modest effects on risk of disease, and only explain a small proportion of familial aggregation of disease. In this study we aim to identify rarer genetic variants that have stronger effects on risk of disease, using new statistical methods and new methods to sequence very large amounts of DNA.
Identification Of Novel Therapeutic Binding Sites On Glycine Receptors By High Throughput Screening
Funder
National Health and Medical Research Council
Funding Amount
$542,017.00
Summary
Glycine receptors mediate inhibitory neurotransmission in the nervous system. They provide fresh therapeutic targets for chronic inflammatory pain and muscle spasticity. Here we identify 5 compounds that may be appropriate as leads for discovering novel therapies for these disorders. We will use automated high throughput screening methods to discover how these drugs interact with the receptor. This will narrow down the search for the next generation of analgesic and muscle relaxant drugs.
Dissecting The Contribution Of Malaria Translocon Components To Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$326,583.00
Summary
The malaria parasite exports hundreds of proteins into its host red blood cell via a unique protein export machinery. This enables the parasite to avoid immune detection, resulting in over one million deaths annually. This proposal will use a rodent malaria infection model to address the functional significance and contribution of the machinery to malaria disease to discern if it will provide a potential target for anti-malaria drugs.
Splice Correction As A Treatment For Rare Diseases
Funder
National Health and Medical Research Council
Funding Amount
$824,316.00
Summary
We propose that a strategy of bringing effective and personalised treatments to amenable patients with rare genetic diseases, though ambitious, is readily achievable and opportune. Importantly, a consensus approach will facilitate expediting potentially curative treatments for many patients with rare diseases that would be unlikely to be commercially viable if considered individually.
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.
FANC Gene Mutations In Acute Myeloid Leukaemia Biology And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$900,780.00
Summary
We have found mutations in DNA repair genes in AML patients, and associated the presence of these with increased risk of developing AML. Our hypothesis is that the presence of these mutations leads to reduced efficiency of DNA repair, and increased risk of additional mutations and leukaemic transformation. Our aim is therefore to determine the changes associated with these mutations in blood cell precursors, and to investigate the potential of targeted therapies for this group of patients.