Targeting Dysfunctional Mitochondria In Macrophages To Inhibit Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$1,009,796.00
Summary
The major contributing cells to heart disease are macrophages. These cells scavenge cholesterol, keeping the blood vessels clean and limiting heart disease. The macrophages must process and donate the scavenged cholesterol onto HDL-cholesterol that carries them back to the liver for removal. This process requires the powerhouse of the cell, the mitochondria to be functional. We have discovered that process fails and have novel drugs to re-instate this process of cholesterol removal.
Regulation Of Immune Responses In The Adult Testis And Male Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$637,857.00
Summary
This project investigates the main inflammatory cell, the macrophage, in male fertility and reproductive health. These studies investigate the macrophages found in the testes and the regulation of their functions required to protect and support the developing sperm. Understanding these processes will lead to new methods for treating male infertility, chronic pain and reproductive tract infections, as well as broader understanding of inflammatory disease, transplantation and autoimmunity.
A Helminth-derived Peptide Is A Novel Prophylactic And Therapeutic Treatment For Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$658,778.00
Summary
Parasitic worms (helminths) secrete molecules that possess a remarkable ability to skew the mammalian immune system towards anti-inflammatory responses. We have expoited a novel peptide secreted by helminths, which offers tremendous potential for the development of novel prophylactic and therapeutic treatments for a range of immune-mediated conditions. The overarching aim of this project is to further elucidate the mechanism of action and to determine the peptide’s clinical application.
Reprogramming Macrophage Function In The Elderly To Rescue Impaired Inflammatory Responses To Muscle Injury
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Muscle injury in the elderly often takes longer to heal than in younger people, however the cells responsible for this delayed healing are not well understood. Key inflammatory cells required for muscle repair in young hosts are macrophages. However, during aging we have shown that macrophage function is altered, but the mechanism is unknown. This project aims to determine the mechanisms behind age-related changes to macrophages and whether they can be targeted to improve elderly muscle repair.
The Role Of Perivascular Macrophages In The Regulation Of CNS Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Inflammation of the central nervous system can have deleterious consequences. How the inflammatory cascade operates within the CNS is poorly understood. We have recently discovered a novel subset of immune cells, the perivascular macrophage, which regulates the recruitment of inflammatory cells. Aim of this proposal is to dissect the role of these cells during brain infections and autoimmune inflammation.
Male Chlamydia Infections: The Key Role Of Macrophages In Testicular Dissemination And Disrupted Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$868,464.00
Summary
Male partners of couples seeking IVF, who are seropositive for Chlamydia, indicating a prior infection, often have significantly impaired sperm quality (reduced motility, increased DNA damage and abnormal sperm morphology). Our studies will define how Chlamydia are transported to the testis from the penis and how chronic chlamydial infection in the testis disrupts sperm development. We will also develop new antibiotic delivery systems to improve treatment of male chlamydial infections.
Defining The In Vivo Contribution Of Leukocyte Extracellular Traps To Infective Disease
Funder
National Health and Medical Research Council
Funding Amount
$598,363.00
Summary
Neutrophils are the white blood cells that protect against infection. A surprising protective neutrophil behaviour was recently described – neutrophils can pack up their internal DNA and antimicrobial enzymes and explosively release them into their surrounds, forming a “Neutrophil Extracellular Trap” (NET). This project uses zebrafish built have fluorescent neutrophils to study NET release in living animals. We will learn how NETs control infection and what goes wrong when NETs cause disease.
Osteoarthritis (OA) affects approximately 20% of Australians and costs billions each year in joint replacements. Therapies that halt joint destruction in OA are urgently needed. We hypothesise that the little-known gene, vanin -3, is a key regulator of OA disease pathways. Our project will map vanin-3 in the joint and reveal how much vanin-3 contributes to joint destruction in mice. We expect to find a link between vanin-3 and metabolic disorders and identify new targets for therapy.
The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
Understanding And Applying Macrophage-mediated Effects On Liver Progenitor Cells To Treat Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$628,109.00
Summary
As liver cancer risk correlates with increased liver stem/progenitor cell numbers, therapies that reduce their numbers will reduce cancer development. On the contrary, therapies to increase progenitor cell numbers will assist their use in cell therapy-based approaches or artificial liver devices to treat chronic liver disease. This project will determine how to use inflammatory cells to manipulate progenitor cell numbers.