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
Epigenetic Mechanisms That Regulate B Cell Differentiation And Memory B Cell Persistence To Provide Long-term Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$318,196.00
Summary
Memory immune cells remember antigens that have previously induced an immune response, and the ability of these cells to rapidly clear pathogens has led to successful vaccination programs. This project will study epigenetic changes during the formation of immune memory that results in protection against foreign antigens. Understanding these processes will assist in creating more effective vaccines and treatments for patients with immune disorders.
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
Defining The Stage Specific Requirements For Bcl-2 Family Members In The Development And Maintenance Of B Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Both vaccinations and pathogenic infections provoke an immune response. Our immune system ñmemorizesî this response, enabling a faster and stronger reaction upon re-encounter. This memory requires specialized cells of the immune system, some of which secrete antibodies and some of which patrol the body. Remarkably, these cells can live for decades in humans and provide immunity. In this project we will study the roles of specific proteins regulating the generation and survival of memory cells.
Many of the most serious diseases of Western societies including obesity, Type 2 diabetes, cancer growth and metastasis and cardiovascular disease have metabolic dimensions. The enzyme AMPK regulates cellular and whole body energy homeostasis by coordinating metabolic pathways to balance energy demand with nutrient supply. We are studying the structure and function of AMPK with the aim of better treating metabolic diseases.
Resolving And Targeting The Complex Molecular Mechanisms Underlying GPCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,071,370.00
Summary
Receptors are located on the surface of all human cells to allow our cells to respond to their environment. Over 30% of prescription drugs act through particular receptors called GPCRs, however effective drugs without side effects are difficult to develop because we do not have a deep understanding of how GPCRs transmit complex signals. In this proposal we seek to resolve the atomic-level details of GPCR signalling to assist in the development of better drugs for a diverse range of diseases.
Waxing And Waning Of Asthma During Transition From The Teens To Adulthood: Identification Of Immunophenotypic Markers To Predict Disease Trajectory And Guide Development Of Treatment Strategies To Prevent Progression To Chronicity
Funder
National Health and Medical Research Council
Funding Amount
$736,166.00
Summary
The project will seek to identify biomarkers in teenage/young adult asthmatics that can distinguish between those who are "growing out" of the disease, versus those who are progressing towards chronic severe asthma. This knowledge will inform the development of more effective treatment programs for this age group.
Computational Reconstruction And Validation Of A Gene Regulatory Network Controlling Differentiation Of B Cells To Antibody-secreting Plasma Cells
Funder
National Health and Medical Research Council
Funding Amount
$618,152.00
Summary
Regulation of B cell differentiation, which occurs when our body responds to antigen infection is tightly controlled by a gene regulatory network. This project will be the first study to reconstruct a regulatory network for this process by using genome-wide expression and transcription factor binding data. The research finding from this study will elucidate the molecular mechanisms regulating this process and will shed new light on how this network is altered in lymphoma and myeloma.
Design And Delivery Of Peptide-based Anti-cancer Grb7 Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The Grb7 protein is overproduced in many types of cancer cells and plays a role in cancer cell growth and spread. The current proposal builds upon the discovery of a peptide-based Grb7 inhibitor that has anti-cancer activity. This proposal is to prepare more potent inhibitor molecules that can efficiently reach the target cancer cells. Such molecules will be used for the study of Grb7 and for the development of a new Grb7-based anti-cancer drug therapy.
Correlating Multiple Sclerosis Risk SNPs With Immune Cell Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$789,386.00
Summary
In Multiple Sclerosis (MS), the immune system repeatedly attacks the brain and spinal cord. In the last three years, rapid progress has been made in understanding genetic risk factors for MS, and more than 20 are known, but their function is not understood. The proposed study will recruit patients with MS and healthy controls to isolate five major immune cell types, and will assess how risk genes influence these cells. We hope to obtain a much better picture of how genetic risk factors for MS ac ....In Multiple Sclerosis (MS), the immune system repeatedly attacks the brain and spinal cord. In the last three years, rapid progress has been made in understanding genetic risk factors for MS, and more than 20 are known, but their function is not understood. The proposed study will recruit patients with MS and healthy controls to isolate five major immune cell types, and will assess how risk genes influence these cells. We hope to obtain a much better picture of how genetic risk factors for MS actually work.Read moreRead less