Neuroimmunology and Remyelination
We are multi-disciplinary group straddling the fields of neuroinflammation, genetics and myelin biology, with a particular interest in the intersection of these disciplines in multiple sclerosis (MS) susceptibility, severity and recovery. Our team works collaboratively to investigate questions ranging from basic biology, such as the effect of receptor tyrosine kinases on myelination by oligodendrocytes, through to translational research, developing novel therapeutic treatments for MS. We use a variety of techniques and mouse models of MS, as well as directly studying the human disease. We have a number of projects available that are suitable for both Honours. Masters and PhD students.
Microglia and myelin development and repair
Microglia, innate immune cells which are exclusively found within the central nervous system, are often activated during the clinical course of MS. Microglia can be either pathogenic or reparative; the latter having a key role in phagocytosis of myelin debris and therefore providing an environment receptive to remyelination. It has recently been identified that Mertk, a cell surface receptor that mediates the phagocytosis of cellular debris, is exclusively expressed by reparative anti-inflammatory microglia.
We have a number of projects available to further examine the role of Mertk in microglial development, and during myelin repair following a demyelinating event:
Michele Binder firstname.lastname@example.org
Project 1: The role of Mertk during microglial development in the brain
We have evidence that the cell-specific deletion of Mertk from microglia results in the production of abnormal myelin by oligodendrocytes (the myelin-producing cells of the brain). The aim of this project is to undertake a detailed examination of the number and proliferation of Mertk-expressing microglia in white matter regions, and the relationship of these cells to oligodendrocytes and myelination. This will allow us to better understand when and where Mertk is expressed during the course of developmental myelination. In order to do this, we will utilise mice in which microglia express green fluorescent protein (GFP), and compare the development of microglia in which we have deleted the Mertk gene with normal microglia.
We have previously shown that the number of Mertk-expressing microglia is increased during the course of demyelination in a mouse model of MS, and that loss of the ligand for Mertk worsens outcome during demyelination, and delays repair. This project aims to determine the influence of Mertk-expressing microglia upon myelin repair. To do this we will compare the extent of myelin repair and cellular responses in mice in which we have specifically deleted the Mertk gene from microglia, compared with normal mice.