Genotypes And Phenotypes Of Human Primary Non-congenital Antibody Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$544,692.00
Summary
Antibodies represent a key component of the immune system, and a particularly important in defence against bacterial and viral infections. In some individuals, antibody production fails, rendering them more susceptible to infection. In most cases, the mechanism of antibody failure is unknown. This project seeks to determine the genetic and cellular mechanisms of antibody failure. This could improve diagnosis for immune deficiency, and improve our overall understanding of the immune system.
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.
An Alternate Function Of The MicroRNA Biogenesis Machinery
Funder
National Health and Medical Research Council
Funding Amount
$302,981.00
Summary
Controlling the activity of genes is crucial. Too much or too little can result in a cell not functioning properly. We have discovered a new way genes are controlled. We have found that an enzyme called Drosha can prevent too much activation of some genes by chopping up the products of these genes. This way of controlling genes appears to be especially important for developmental processes, such as occurs in the embryo. Our goal is to understand this mechanism precisely at the molecular level.
Growth Factors And Their Effect On MicroRNAs And Transcription Factors In Tubulointerstitial Fibrosis In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$490,202.00
Summary
A common cause of kidney disease is diabetes and is partly related to increased expression and action of growth factors such as CTGF. These factors promote the deposition of scar tissue in the kidney by acting on a novel class of intracellular regulator molecules called microRNAs, to change the cell's characteristics such that cells begin laying down excess collagen. This proposal will focus on how growth factors act on microRNAs and the role of microRNAs in diabetic kidney disease.
TGFB1 Is A Pivitol Regulator Of Endometriotic Lesion Development
Funder
National Health and Medical Research Council
Funding Amount
$438,749.00
Summary
Endometriosis occurs when the tissue that lines the womb is found in the pelvic cavity. 10% of reproductive aged women have endometriosis and suffer from debilitating pelvic pain and subfertility. We have shown that transforming growth factor (TGFB1) is central to the growth of endometriosis and that its absence suppresses disease development. We hope to clarify the role of TGFB1 in endometriosis, in order to develop better therapeutic options for women incapacitated by this disease.
Regulation Of Expression Of MicroRNAs Involved In EMT
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
The majority of deaths from cancer are due to metastasis, which involves cancer cells becoming invasive and migratory. We aim to understand the molecular mechanisms that control this process, which may lead to identification of molecules that are potentially useful for diagnosing and treating cancer metastasis. We will investigate how TGF� regulates the expression of ZEB proteins, how the ZEB proteins function to repress key microRNAs, and what other genes are targeted by the ZEBs.
In Australia seventeen persons are diagnosed with leukemia or a related blood disorder each day. An understanding of the way the body controls blood cell production has widespread relevance to diseases like leukemia and the way that they are treated. The burden of this disease on the Australian health budget will continue to increase dramatically as our population ages in coming years. Moreover, an understanding of blood cell production has wider relevance to similar control mechanisms in other ....In Australia seventeen persons are diagnosed with leukemia or a related blood disorder each day. An understanding of the way the body controls blood cell production has widespread relevance to diseases like leukemia and the way that they are treated. The burden of this disease on the Australian health budget will continue to increase dramatically as our population ages in coming years. Moreover, an understanding of blood cell production has wider relevance to similar control mechanisms in other organs, as nature reuses its best inventions. Australia has had an enviable international record in discoveries related to factors controlling blood cells and we wish to continue that tradition by examining an exciting new development involving microRNAs. These molecules are found in all normal cells but they have been ignored until recently. Although the field is in its infancy, we now know that these microRNAs are likely to be involved in many cellular processes. In this project we will study the importance of this new class of regulatory molecule in order to discover previously-hidden functions in normal blood cells and their malignant counterparts (leukemias) in humans. The team comprises two laboratories which have collaborated for many years and already a number of exciting molecular methods have been developed. Ultimately this project may lead to novel treatments involving gene therapy, bone marrow transplantation and blood hormones.Read moreRead less
MICRORNA PREDICTORS OF OESOPHAGEAL TUMOUR RESPONSE TO CHEMOTHERAPY AND RADIOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$659,990.00
Summary
Chemoradiotherapy (CRT) is used for the treatment of oesophageal cancer before surgical resection, and for patients not undergoing surgery. However, it is unsuccessful for many, causing side effects, no clinical gain, and delaying surgery. MicroRNAs are small molecules that control cellular functions. This project will identify miRNA markers which are able to predict cancer response to CRT, and this will help clinical decision making for individualized treatment.
PI3K-regulated Heat Shock Proteins And MicroRNAs As New Treatment Strategies For Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$553,633.00
Summary
Atrial fibrillation (AF) is the most common sustained arrhythmia presenting in cardiology departments worldwide and is associated with increased mortality and morbidity. New treatment strategies are greatly needed. We have discovered that lower levels of a gene with protective properties in the heart causes AF in mice and is associated with AF in humans. This proposal will examine whether novel agents that target this gene can reduce or prevent AF.
Identification And Functional Evaluation Of MicroRNAs And Their Target Genes That Regulate Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$607,773.00
Summary
Breast cancer is the major cause of cancer-associated death in Australian women. Once the disease has spread to other organs, as occurs in about 20% of cases, our ability to treat the disease is limited and mortality is high, leading to an enormous social and economic cost New therapies for advanced disease are needed urgently. To facilitate this, we need to understand the molecular regulation of metastasis to distant organs and use this knowledge to develop new molecular targeted therapies.