Quick Project Snapshot
The role of P2X7 in a mouse model of oligodendrocyte apoptosis
Oligodendrocytes support the function of nerve cells by producing a fatty substance called myelin that insulates the axons of nerve cells, much like plastic insulation around an electricity cable. Dying (apoptotic) cells are normally cleared from the brain by specialised scavenger cells called microglia that engulf and digest them. Previous studies of our group have shown that the P2X7 protein found on the surface of these scavenger cells recognizes the dying cells and helps their engulfment. If dying cells are not removed, they leak molecules causing inflammation of the brain, which worsens symptoms of neurological disorders. It appears that P2X7 is important in limiting the extent of this neurodegeneration in MS since genetic variations in P2X7 in humans can confer either an increased risk or protection against developing MS. In this project, we will investigate the role of P2X7 in regulating the ability of microglial to remove dying oligodendrocytes from the brain using an established mouse model. The results will provide insight on the role that P2X7 plays in orchestrating the inflammatory response to oligodendrocyte death. This knowledge will aid in our long-term goal of developing methods to protect neurons from permanent damage. Techniques involved are small animal handling, tissue collection, immunohistochemical staining, cell culture, flow cytometry.
Innate Phagocytosis Laboratory
The Innate Phagocytosis Laboratory led by Dr. Ben J. Gu and Prof. James S. Wiley has great interests in discovering the role of innate phagocytosis in neurodegeneration, neurodevelopment, infection and cancer. This Lab has a long history of studies on the P2X7 receptor, an ion channel activated by ATP. They discovered the non-functional P2X7 and identified a number of genetic variations affecting P2X7 pore formation and pro-inflammatory responses. Recently they have found that P2X7 is in fact a scavenger receptor in the absence of ATP or serum. Further study of P2X7 mediated innate phagocytosis opens a new research field for its role in broad biological aspects, including:
- Neurodegeneration: This lab explores genetic, cell biological and animal studies to identify a common mechanism underlying a number of neurological disorders including Alzheimer’s disease, age-related macular degeneration and multiple sclerosis.
- Neurodevelopment: This lab has revealed that P2X7 mediated phagocytosis probably contributes to the early development of central nervous system by removing apoptotic neuronal cells.
- Infection: Innate immunity can be promoted by neutralizing certain glycoprotein in serum or by compounds promoting innate phagocytosis. This lab is currently developing a rabbit model of bacteraemia/sepsis.
- Cancer: The non-functional P2X7 is found to be expressed on the surface of various tumor cells, but not on normal cells. The antibody against this non-functional P2X7 receptor is currently undergoing a clinical trial for basal cell carcinoma conducted by Biosceptre Pty Ltd. This lab has great interests in investigating the biological nature of non-functional P2X7, P2X7 mediated phagocytosis and oncogenesis.
All Projects by this LabSearch the P2X7 related biomarkers for Alzheimer’s diseaseThe nature of the P2X4 receptorThe role of P2X7 in a mouse model of oligodendrocyte apoptosisInvestigation of P2X7 mediated phagocytosis - potential therapeutic target for cancer treatmentIdentify the transcriptional regulatory factors of the P2X7 receptorHow does the brain remove the excess number of neurons during development and agingIdentification of serum glycoproteins altering innate immunityDo circulating microvesicles from patients with multiple sclerosis (MS) disrupt the blood-brain barrier (BBB)? (For Honors and MBiomedSc)The Role of Innate Phagocytosis in the Pathogenesis and Treatment of Alzheimer's Disease (for PhD only)
The Florey's Epilepsy division is a world-leading centre for epilepsy research. The division has major groups at both the Florey’s Austin and Parkville campus. The group studies mechanisms that cause epilepsy from the level of cells to the function of the whole brain. We use technologies including advanced MRI and cutting edge cellular physiology techniques to allow us to understand genetic and acquired mechanisms that give rise to epilepsy. Together with our colleagues from The University of Melbourne and across Australia we are working towards finding a cure for epilepsy.