THE PATHOGENIC AND PROTECTIVE EFFECTS OF MICROGLIA IN CEREBRAL CYTOKINOPATHIES

Summary

Microglia are the primary immune cells of the brain and have the potential to both protect and contribute to neurological disease. Explore the molecular mechanisms that microglia use to mediate their biological effects in cerebral cytokinopathies. 

Supervisor(s)

Dr Markus Hofer

Research Location

School of Life and Environmental Sciences

Program Type

Masters/PHD

Synopsis

The cytokines interleukin-6 (IL-6) and interferon-alpha (IFN-alpha) can cause a variety of neuroinflammatory diseases such as neuromyelitis optica and Aicardi-Goutières syndrome or neurological manifestations of systemic lupus erythematosus, respectively. They also are implicated in the development of a number of significant age-related neuropsychiatric disorders. However, an understanding of the mechanisms via which these cytokines mediate central nervous system (CNS) damage is unclear. Transgenic (TG) mouse models with CNS-restricted chronic production at pathophysiologically relevant levels of IL-6 or IFN-alpha replicate many of the key neuropathological and behavioural features of the human diseases, further highlighting the role of these cytokines as mediators of CNS injury and disease. Microglia, the innate immune cells of the CNS, are highly responsive cells that assume a variety of phenotypic states depending on the context of the surrounding environment. The activation of these cells is an early and pervasive feature of neurological and neuropsychiatric disease. Importantly, the actions and outcomes of transgenic IL-6 and IFN-alpha production in the brain are distinct, making these models also an ideal tool to study, and compare and contrast the responses and functions of microglia in the living brain. While the role of microglia in the pathogenesis of human disease is enigmatic, previous work by us implicate microglia as both a major target of and effector cell for IL-6 and IFN-alpha. Consequently, the overarching hypothesis driving this project is that microglia are central cellular effectors in many of the clinicopathological actions of IL-6 and IFN-alpha in the CNS.

Additional Information

HDR Inherent Requirements

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

- Confidential disclosure and registration of a disability that may hinder your performance in your degree;
- Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
- Ability to perform independently and/or with minimal supervision;
- Ability to undertake certain physical tasks (e.g. heavy lifting);
- Ability to undertake observatory, sensory and communication tasks;
- Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
- Ability to work in confined spaces or at heights;
- Ability to operate heavy machinery (e.g. farming equipment);
- Hold or acquire an Australian driver’s licence;
- Hold a current scuba diving license;
- Hold a current Working with Children Check;
- Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

Keywords

type I interferon; neuroinflammation, type I interferonopathies; neuroscience; immunology; microglia; brain; CNS; inflammation; neurodegeneration; interleukin-6; IL-6; interferon; mouse model; transgenic;

Opportunity ID

The opportunity ID for this research opportunity is: 2703

Other opportunities with Dr Markus Hofer

• TARGETING THE BRAIN VASCULATURE AS A TREATMENT FOR CEREBRAL TYPE I INTERFERONOPATHIES
• HOW DIFFERENT CELL TYPES OF THE BRAIN CONTRIBUTE TO CEREBRAL CYTOKINOPATHIES
• EFFECTS OF TYPE I INTERFERONS IN CHRONIC VIRAL INFECTIONS
• Maternal autoimmunity increases risk of neurodevelopmental problems in offspring.