Investigation And Modulation Of RANKL-induced Osteoclastogensis, Bone Resorption And Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$33,825.00
Summary
Osteoclasts are exclusively responsible for the degradation of bone matrix. RANKL is a member of a ligand-receptor system which directly regulates osteoclast differentiation and bone resorption. New treatment regime for various bone diseases have been highly sought after for many years. The identification of potential natural compounds that inhibit the formation and function of osteoclasts might serve as a useful tool for such treatment.
Investigating The Roles Of Non-coding RNAs In Inflammatory Signalling And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Inflammation occurs as part of the body's natural defenses against infection or injury, but can be damaging when unregulated and can lead to cancer. Although the protein factors critical for inflammation have been carefully studied it remains unknown how ribonucleic acid (RNA) molecules can modify and regulate inflammation. This project will identify RNA molecules that control inflammatory signalling, and further translate these findings to show they contribute to the progression of cancer.
Simvastatin Prevents Dopaminergic Neuronal Injury In Experimental PD Models Via Activation Of NF-kB And MMP 9 And 3
Funder
National Health and Medical Research Council
Funding Amount
$87,937.00
Summary
Increasing evidence shows that neuroinflammation may account for dopamine neuron death in Parkinson’s disease (PD). This work aims to provide systematic picture of inflammatory response in PD, and explore anti-inflammatory mechanisms of simvastatin on the progression of PD. We expect that the results may provide a therapeutic strategy using simvastatin via different methods of administration in treating PD, and provide new information about the anti-inflammatory roles of simvastatin.
Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
Rotavirus is the main cause of severe diarrhoea in children worldwide. In this project, we aim to understand the nature of the first-line immune response to rotavirus in the gut, and elucidate how RV counteracts this response to promote infection. These studies will increase our understanding of how rotavirus causes disease, and facilitate the choice of rotavirus targets for drug development and improved vaccines.
Determining The Role Of Rel/NF-kB Transcription Factors In Myeloid Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$500,944.00
Summary
Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB ....Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB proteins, a change in the pattern of gene expression in GMPs leads to an imbalance in production of these two blood cell types that now favours the generation of neutrophils. This work will provide insight into the molecular mechanisms of blood cell development regulated by NF-kB. With disturbances in the balance of blood cell formation representing a hallmark of leukemia, understanding how this process is normally controlled may have important implications for developing therapeutic strategies to combat various types of leukemias.Read moreRead less
We have generated mice with symptoms mirroring the inflammatory bowel disease, ulcerative colitis (UC). These mice have mutations in the gene producing the major component of the protective mucus layer in the intestine. The mutations lead to a phenomenon known as ER stress. We have shown that ER stress also occurs in UC, opening up a new understanding of this disease. The proposed research will explore links between ER stress and inflammation and test potential new treatments for UC.
Determining The Role Of Rel/NF-kB Transcription Factors In CD8 T Cell Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur f ....NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur frequently and therefore there is an even greater need to understand how the immune system may be affected or compromised in response to the primary treatment. This work will provide insights into the cellular and molecular mechanisms affected by the absnece of a particular NF-kB family member (NF-kB1) in CD8 T cells during normal T cell homeostasis and when challenged with viruses. What we learn from our experiments could have important implications for the development of vaccines.Read moreRead less
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?
Roles Of Signalling In The Control Of Immune System Development, Function And Pathology
Funder
National Health and Medical Research Council
Funding Amount
$737,936.00
Summary
This research focuses on the function of the NF-?B and MAP kinase biochemical pathways in immune cells. Both pathways regulate gene expression controlling the development, division, viability and function of immune cells. Consistent with these roles, impaired regulation of these pathways contributes to many immune related diseases. My goal is to utilize information learnt about these pathways and apply it to developing therapies for treating diseases afflicting the immune system.