The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Identification Of The Conformation Dependant Targets Of Autoimmune Disease Linked Variation In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,001,815.00
Summary
Specialised immune cells called regulatory T cells act as the policemen of the immune system, preventing the immune system attacking itself, but still fighting infections. If these cells do not work properly, autoimmune diseases such as type 1 diabetes or IBD can arise, because of immune attack on normal body tissue by mistake. In order to explain how this goes wrong we need to carefully identify all of the gene interactions in these cells including interactions over long distances in the DNA.
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
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.
Characterising Signals Important For Lymphangiogenesis During Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$604,938.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including cancer, lymphoedema and inflammatory diseases. The focus of this application is to characterise signals that direct the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
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.
Preclinical Development Of TLR Signalling Inhibitors For Prevention Of Preterm Labour And Fetal Inflammatory Injury
Funder
National Health and Medical Research Council
Funding Amount
$690,821.00
Summary
Preterm birth affects 8% of Australian births and is a major cause of infant and child health problems. Therapies to prevent or delay prematurity are urgently required. This study will investigate new drugs that suppress the triggers of preterm labour. We will evaluate drug effects in mice and human placental tissue, to demonstrate safety and fetal protection from inflammatory injury that occurs with prematurity. Successful completion of the study is expected to lead to clinical trials in women.
Understanding How GATA2 Controls Lymphatic Vessel Valve Development
Funder
National Health and Medical Research Council
Funding Amount
$697,942.00
Summary
Mutations in the GATA2 gene cause human lymphoedema as a result of the crucial role that GATA2 plays in controlling the expression of genes important for building functional lymphatic vessels. Here we aim to gain a complete picture of the cellular and molecular events that are controlled by GATA2 in lymphatic vessels and in particular, in lymphatic vessel valves.
Multistage Vaccines For The Prevention Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$884,290.00
Summary
Almost two million people die from tuberculosis (TB) each year. The current vaccine, BCG, is ineffective at controlling TB and the type of immune response needed to protect against the disease is poorly understood. We have discovered new antigens of the TB bacterium, and we will combine them with novel delivery strategies to develop new TB vaccines. We will also determine the type of immune response needed to protect against TB, which will aid progression of vaccines into clinical trials.