Using MiR-200 To Find New Therapeutic Targets For Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$563,152.00
Summary
Neuroblastoma is one of the most common cancers in children. We have found that a genetic regulator, called microRNA, can limit the ability of neuroblastoma cells to invade surrounding tissues and metastasise. We aim use the microRNAs to find new therapeutic targets that may work in combination with existing treatments, reducing the short term toxicity and long term deleterious effects of current treatments.
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
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.
Role Of The MiR-200 Target Quaking In Alternative Splicing During EMT And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$443,160.00
Summary
The spread of cancer to other organs involves cancer cells changing to a more aggressive state and is a major cause of cancer related death. MicroRNAs are a class of genes that control whether cancer cells become more aggressive by regulating other genes. In this project we will examine the function of a new microRNA target which controls the cancer cell aggression. The outcome will be a better understanding of how cancers spread and the identification of new therapeutic targets.
Characterising Novel Alternative Splicing Networks That Promote Tumour Cell Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$609,329.00
Summary
During cancer progression, tumour cells can change their properties and become more aggressive and resistant to therapies. We have identified an important regulator of this tumour cell transition, called “Quaking”, which causes widespread changes in gene splicing. We aim to investigate how "Quaking" causes changes in gene splicing and what the effects of these splicing changes are in tumour cells.
The migration of cancer cells (metastasis) is responsible for most cancer deaths. Central to this is dynamic organisation of the actin cytoskeleton _ an internal structure that provides cell shape and enables movement. We have identified a family of small molecules (called miR-200) that regulates this actin cytoskeleton through specifically downregulating various genes. We are investigating the nature of these genes and their role in cell motility _ an underlying pre-requisite of metastasis.
Male-female Sperm Signalling - A Novel Pathway For Peri-conceptual Health?
Funder
National Health and Medical Research Council
Funding Amount
$674,920.00
Summary
This project will investigate a new biological process in reproduction, whereby sperm delivered to the cervix at coitus transmit signalling molecules called microRNAs that influence the female immune response, to increase the chances of conception and pregnancy. We will define the molecular details of this signalling pathway in mouse models, and then determine whether human sperm have a comparable function in ‘priming’ the female body to conceive.