Pathways That Regulate Nuclear Export Of Circular RNA
Funder
National Health and Medical Research Council
Funding Amount
$933,327.00
Summary
An emerging and unusual class of RNA molecules, circular RNAs (circRNAs), is widespread and plays important roles in cancer initiation and progression. However, the pathways responsible for nuclear export of circRNAs are unknown. We propose here to systematically determine how circRNAs are exported from the nucleus and characterise the effect of modulating circRNA export pathways in cancer. This will enable us to determine whether circRNAs can function as a biomarker of patient response.
Exploiting Messenger RNA Export As A Novel Therapeutic Strategy To Treat Cancer
Funder
National Health and Medical Research Council
Funding Amount
$948,098.00
Summary
Novel therapies for cancers represent an area of unmet clinical need. We have identified a new biological pathway implicated in cancer, namely selective mRNA export. Compounds inhibiting other steps of the gene expression pathway are promising therapeutic candidates for cancer, yet mRNA export inhibitors do not exist. We propose to develop first-in-class inhibitors of mRNA export that selectively target transcriptionally addicted cancers with dysregulated RNA processing.
Long Noncoding RNA In Space And Time, And The Regulation Of Fear Extinction
Funder
National Health and Medical Research Council
Funding Amount
$1,012,245.00
Summary
Most of our genome is made up noncoding RNA; however, nothing is known about why a special class of noncoding RNA would be expressed in synapses, and how this affects learning and memory related to neuropsychiatric disorders. Understanding the fundamental molecular machinery underlying the formation of fear extinction memory will enable the development of new treatment approaches for anxiety-related disorders that are characterised by memory deficits.
Dissecting Brain Network Ageing Using Whole Brain Imaging
Funder
National Health and Medical Research Council
Funding Amount
$692,964.00
Summary
In this proposal, we will make the first attempt to map the whole brain activity change during ageing using a series of state-of-the-art techniques. We will also identify genetic and pharmacological interventions that improve brain network function during ageing. Outcomes from this research will provide an unprecedented understanding of functional ageing within the brain and identify therapeutic interventions to prevent this process.
The Role Of LINE Encoded Natural Antisense Transcripts In Immune Regulation
Funder
National Health and Medical Research Council
Funding Amount
$934,853.00
Summary
Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. This proposal aims to utilize cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes in human autoimmune disease.
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Casting The Net: A New Approach To Identify Therapeutics To Treat Type-2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,068,283.00
Summary
The discovery of treatments for type-2 diabetes (T2D) is a national health priority. In T2D, cells in the brain become 'insulin resistant' resulting in dangerously high blood sugar levels. There are no treatments for brain insulin resistance. The extracellular structures that surround brain cells undergo change in T2D, resulting in insulin resistance. By furthering understanding of these extracellular brain structures, this proposal will identify new drug targets to treat T2D.