In multiple sclerosis (MS), cells of the immune system invade the brain and spinal cord and cause tissue damage that leads to reduced brain and spinal cord function. Potential new treatments include drugs that block these immune cells from moving into the brain and spinal cord.
In this project, Ms Megan Monaghan will investigate markers on the surface of immune cells called CD4+ T cells. These markers, called chemokine receptors, help immune cells travel to areas of inflammation, infection, and injury and respond. She is particularly interested in whether they are Th17 cells, a specific type of immune cell that causes damage.
Ms Monaghan will also use cutting-edge technology to create a detailed picture of the type of CD4+ T cells that infiltrate the brain and spinal cord.
This information will be invaluable for designing next-generation therapies that selectively block inflammatory T cells from moving into the brain in MS.
By understanding how CD4+ T cells are directed into the brain and spinal cord, it may be possible to block only those that cause disease and leave healthy immune cells unaffected. This would help improve MS treatments, where current treatments can also suppress normal immune function, leading to serious side effects.
To do this, Ms Monaghan studied a laboratory model of an MS-like disease and examined individual cells to see which molecules they were producing. She found that disease-causing CD4+ T cells produce higher levels of responder molecules involved in cell movement. One of these responder molecules allows the T cells to respond to a “chemical attractant” that helps guide them to specific locations in the body. Ms Monaghan showed that the responder molecules are especially high in the harmful Th17 cells and may play an important role in drawing them into the brain and spinal cord.
Next, Ms Monaghan used another technique to study the attractants. She found that the attractant molecules are released from the damaged areas of the spinal cord, along with a second signal that is known to attract highly inflammatory immune cells. She also saw that CD4+ T cells in these areas communicate with the surrounding tissue using this attractant-responder system. This suggests the signals are important for pulling harmful Th17 cells into the spinal cord. Ms Monaghan found that dendritic cells – a type of immune cell that helps direct immune responses – were often located close to these CD4+ T cells and were producing large amounts of the attractant. This suggests that dendritic cells may help attract harmful cells into inflamed areas.
In addition, Ms Monaghan discovered that when a particular regulating molecule was missing, the guiding signals were disrupted.
Alongside her work on immune cells and their signals, Ms Monaghan used computer-based methods to screen more than 19 million drugs to identify which could specifically block these disease-causing cells. Promising candidates can then be tested in her laboratory disease model.
Ms Monaghan has submitted a paper to a scientific journal on this project. Over the next 12 months, Ms Monaghan will continue her analyses of the molecules that make disease-causing CD4+ T cells move into the brain and spinal cord. This will allow her to test blocking the production of these molecules in a laboratory disease model. She will also continue her computer-based screening of potential drugs to test in her model. In addition, she will further investigate how the regulating molecule interacts with the attractant and how this changes during disease progression.
Last updated 31 March 2026
Dr Ian Comerford
Professor Shaun McColl
Dr Stephen Pederson
$105,000
2024
3 years
Current project
