Modulating Inflammatory And Fibrogenic Pathways In Kidney Disease Using A Novel Antagonist Of Protease-Activated-Receptor-2
Funder
National Health and Medical Research Council
Funding Amount
$581,116.00
Summary
Chronic kidney disease (CKD) now affects 10% of adults in industrialised countries. Current treatments are largely ineffective. Thus developing better CKD treatments will have substantial public health benefit. Three well established and clinically relevant animal models of kidney disease will be used to test the ability of a new experimental anti-inflammatory drug, developed by members of this research team at The University of Queensland, to prevent or lessen the progression of CKD.
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.
Epigenetic Regulation Of Self Renewal And Lineage Commitment In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$1,104,930.00
Summary
The process by which all our mature blood cells are produced and sustained remains largely unknown. Underpinning the cell fate decisions made through blood cell development is the tightly regulated expression of key genes and proteins that subsequently direct the process of blood cell differentiation. This project will aim study and uncover the molecular mechanisms that coordinate the key gene expression programs that lead to normal blood cell development.
Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related di ....Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related disease.Read moreRead less
Defining The Mechanisms Regulating Tissue Mechano-reciprocity In Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$624,488.00
Summary
Wound healing is slow in people with diseases including diabetes or reduced blood circulation to the limbs. Wounds that remain unhealed for a long time may require surgery and limb amputations, often leading to disability and premature death, while costing the health system $3 billion/yr. We have found that wound healing can be accelerated more than 2-fold by the inhibition of a protein called 14-3-3zeta, and seek to find out how this occurs so that it may be exploited for therapy.
We are seeking to understand how the protein ADAR1 functions. When it is mutated, ADAR1 can cause a range of diseases, most notably in a subset of Aicardi-Goutieres syndrome (AGS) patients, an autoimmune disorder affecting the brain, immune system, and skin. We have identified how we think that changes in ADAR1 activity may ultimately cause disease. This application will allow us to test this mechanism experimentally.
Function And Molecular Mechanism Of Histidine-rich Glycoprotein In Necrotic Cell And Pathogen Clearance
Funder
National Health and Medical Research Council
Funding Amount
$525,957.00
Summary
This research proposal is to investigate the molecular mechanism and function of a blood serum protein, histidine-rich glycoprotein (HRG), in protecting against tissue injury caused by inflammation and infection. HRG has been implicated in controlling important aspects of tissue injury by aiding removal of dead cells and pathogens. Understanding the role of HRG in these disease settings may allow the development of approaches for the treatment of inflammatory, autoimmune and infectious disease.
A New Function For Histone Variants In The Tissue-specific Regulation Of Pre-mRNA Splicing
Funder
National Health and Medical Research Council
Funding Amount
$657,224.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.
Identification And Characterization Of A Novel Long Intergenic Noncoding RNA For The Therapy Of Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Survivors suffer from lifelong disabilities due to chemotherapy. In this application, we will define the role of gene amplification of a long intergenic non-protein-coding RNA in determining the biological effects of a neuroblastoma oncogene, and promoting neuroblastoma initiation and progression. We will also define the anti-cancer efficacy of therapies targeting the long intergenic non-protein-coding RNA.
Long non-coding RNAs (lncRNAs) were considered to be junk, until recently. They cannot make protein so they were thought to be impotent. Despite this dogma, we studied the function of one lncRNA, in detail. Our data suggests it is a master regulator of mesoderm formation, the precursor of all internal organs. In this grant we will determine how this regulator works in normal development and how we might use this knowledge to design new therapies.