Disrupting Mucin-mucin Interactions To Treat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$480,531.00
Summary
Diseases like asthma, emphysema and cystic fibrosis all feature the overproduction of mucus in the lungs that make it very difficult for patients to breathe and increases their susceptibility to infections. Few therapies are available for thinning this mucus, which is made thick by a network of linkages between proteins. We are studying these linkages and developing methods to break them up. This research could yield new mucus-thinning drugs to treat lung diseases.
Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.
A Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.
Development Of New Anticancer Drugs Using Sortase-mediated Ligation
Funder
National Health and Medical Research Council
Funding Amount
$618,274.00
Summary
There is a great need for new cancer treatments. We are developing cyclic peptides as the next generation of safe and effective cancer drugs. Cyclic peptides, unlike their linear counterparts, display high stability and oral bioavailability, as well as high solubility and negligible immune response. One of the hurdles is the cyclisation process and we aim to develop enzyme-mediated cyclisation as a convenient and cost effective method for cyclic peptide production.
Improving Muscular Dystrophy By Targeting The ADAMTS5 Metalloproteinase
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Muscular dystrophy is a devastating childhood disorder. There is no cure and no effective therapy to stop the disease progressing to early death. Our pilot data show that muscular dystrophy in a mouse model is dramatically improved when the Adamts5 gene is inactivated. ADAMTS5 is an enzyme that remodels the extracellular matrix around cells. This suggests that inhibiting ADAMTS5 may be a new way to treat muscular dystrophy. We will test this idea in mice with muscular dystrophy
Is The Role Of IL6 In Metabolism Dependent On Its Cellular Origin?
Funder
National Health and Medical Research Council
Funding Amount
$714,061.00
Summary
Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development f ....Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development for type 2 diabetes.Read moreRead less
Nuclear Retention-and-release Of RNA: A Naturally-occurring Mechanism For Controlling Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$428,753.00
Summary
The deliberate retention of messenger RNA in the nucleus is a newly-discovered biological mechanism used by cells to control which genes are made into proteins, and when. This is a fundamental process in health and disease. The project will employ cutting edge molecular and cellular techniques to discover the principles underpinning nuclear retention. These insights will allow the development of new methods to spatially and temporally control gene expression in diverse gene therapy applications.
Molecular Insights Into Long Noncoding RNA-protein Complexes: Important Gene Regulators In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$388,927.00
Summary
Cancer cells turn good genes off and bad ones on: but how do they do this? Recent breakthroughs suggest that noncoding RNA, produced from so-called ‘junk’ DNA, is important. One such noncoding RNA forms paraspeckles, a novel component of the cell machinery. Here, we will pick apart the way paraspeckles are organised and function, to develop them as a prototype for designing anti-cancer treatments against noncoding RNAs.
Exploring The Role Of MicroRNA And Target Processing Variability In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
microRNAs are gene regulators with critical roles in heart disease. How interactions between microRNAs and their messenger RNA targets change during disease is poorly understood. We hypothesise that these interactions are critically affected by altered processing of microRNAs and targets. We will thus characterise and validate such differences in healthy and diseased hearts. This will define gene regulatory changes underpinning heart disease and contribute to the search for better treatment.
Charting The Interface Between Cellular Metabolic States And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$653,196.00
Summary
The research successes of Molecular Biology and Biochemistry have given us detailed pictures of the regulatory and metabolic states of cells and tissues, yet we know little about how these states affect each other. We hypothesise the existence of regulatory interactions between ribonucleic acids, enzymes and metabolites to connect gene expression and metabolism. We will employ novel RNA Biology methods to discover such regulatory interactions in medically important cellular contexts.