Development Of A Novel Hybrid RAAV/transposon Gene Delivery System For Life-long Correction Of Metabolic Liver Disease In Infants And Children
Funder
National Health and Medical Research Council
Funding Amount
$505,897.00
Summary
The immense potential of gene therapy for the treatment of genetic liver disease has been confirmed by recent success in a clinical trial for Haemophilia in adult males, and therapeutic benefit in other adult trials is imminent using the same technology. In the young, however, ongoing growth of the liver causes the therapeutic benefit to be short-lived. To address this problem we are developing a powerful new hybrid technology capable of conferring life-long benefit on infants and children.
Deciphering Specific Roles For The Common Arnt Proteins In BHLH/PAS Transcription Factor Complexes
Funder
National Health and Medical Research Council
Funding Amount
$526,421.00
Summary
Understanding the precise control of neuronal genes related to appetite and obesity, and neuropsychiatric disorders and dementia, is complicated by some gene regulating proteins having highly related sequences. This project will eludcidate how two closely related proteins can determine specific target gene outputs, information important for designing methods to control activities of neurological disease related genes within cells.
Mechanisms Of Regulating Gene Expression Via Selective MRNA Transport
Funder
National Health and Medical Research Council
Funding Amount
$424,076.00
Summary
A critical step in the gene expression pathway that is altered in cancer is nuclear export of mRNA. We have demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms. This project aims to dissect the molecular mechanisms of regulating gene expression via selective mRNA transport. This will establish selective mRNA export as a novel area of research in cancer biology.
How IsomiRs Expand The MicroRNA Functional Repertoire In Affecting Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$439,570.00
Summary
MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA var ....MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA variation contributes to cancer.Read moreRead less
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less