Multiple sclerosis (MS) is a disease that damages myelin, the protective layer around nerves in the brain and spinal cord. When myelin is damaged, nerve signals don’t work properly, leading to various symptoms.
Unfortunately, there are no treatments that can fully protect or repair myelin. Certain immune cells in the body, like microglia and macrophages, help support myelin-producing cells (oligodendrocytes), but we still don’t fully understand how.
Dr Monokesh Sen and his team believe that tiny particles released by these immune cells, called extracellular vesicles, play an important role in cell communication and may help with myelin repair.
To investigate this, they will collect blood samples from both people with progressive MS (a form of MS with ongoing inflammation, nerve damage and impaired myelin repair) and individuals without MS. From these samples, they will extract immune cells called peripheral blood mononuclear cells, grow them in the lab, and turn them into macrophages. These macrophages naturally release extracellular vesicles (MEVs), which we will collect using a specialised process called ultracentrifugation.
Next, the team will administer MEVs into a laboratory model and track where they go in the body and at the cellular level. They will then test their effects in another MS laboratory model to see how they influence oligodendrocytes and myelin repair.
By understanding how these MEVs affect myelin regeneration, Dr Sen and his team hope to find new ways to repair myelin and develop future treatments that could improve the lives of people with MS.
A person’s risk of developing multiple sclerosis (MS) is influenced by both their genes and environmental factors. Infection with the Epstein-Barr virus (EBV), which causes glandular fever, has been shown to be a necessary step in the development of MS, although most people who contract EBV never go on to develop the disease.
This suggests that differences in how people’s immune systems respond to EBV, which are strongly influenced by genetics, may play an important role in MS risk.
This project will compare EBV, MS, and immune-related measures in people with either a ‘high’ or ‘low’ genetic risk of developing MS. To achieve this, Dr Stacey and the research team will employ an innovative study design called recall by genotype, a method that selects participants based on their genetic risk.
This approach has not yet been used in MS research, either in Australia or internationally. Unlike most studies that compare people with and without MS, none of the participants in this study will have the disease. This means any differences observed are more likely to reflect early biological processes that contribute to MS, rather than changes caused by the disease itself.
The aim of the project is to test how feasible it is to use this approach in MS research and to prepare for a larger study in future. The team will: (i) refine methods for selecting and inviting participants based on genetic risk; (ii) explore the ethical, legal and social implications of using genetic information for research recruitment; and (iii) fine-tune laboratory methods to measure key immune and viral markers.
This work may improve our understanding of how MS develops and could help identify new ways to predict, prevent or treat the disease.
The exact cause and mechanisms underlying the development of multiple sclerosis (MS) are poorly understood, but we know it is driven by a complex interplay between genes and environmental factors.
The genetic risk factors of MS strongly implicate immune cells and vascular cells (cells of the heart and blood vessels) in driving MS initiation. Despite this, few studies have explored the role that vascular cells play in disease development.
Dr Alastair Fortune and his team aim to determine how MS genes can alter pericytes (brain vascular cells) even before immune cell activation can damage them. They will generate pericytes from induced pluripotent stem cells (iPSCs) – immature cells that can produce any cell type in the body – from people with and without MS, and compare their function.
Blood flow is altered in people with MS, and the team will determine whether this is due to DNA-programmed differences in MS pericytes. They will also investigate how pericytes respond to an MS lesion-like environment.
This project aims to determine whether and how pericytes contribute to blood vessel abnormalities in people with MS.
Poor sleep is common in the general population, but it’s even more common among people living with multiple sclerosis (MS). Sleep problems can have a serious impact on health and quality of life, and there is an urgent need for better treatments that improve both sleep and MS symptoms.
Researchers often assess sleep using survey questions, but these can miss important details. Sometimes activity monitors (similar to research-grade Fitbits) are used, but typically only for a week; this might not be long enough for people with MS, whose symptoms can change from day to day. Despite this variability, researchers don’t usually collect symptom information frequently enough to detect these changes.
This project will focus on getting the basics right by collecting high-quality, meaningful data on sleep in people with MS. Dr Laura Laslett’s research will test whether using activity monitors to track sleep and a symptom-tracking app (MySymptoMS) is practical and acceptable for people living with MS. She aims to find out whether these tools need to be used for longer than a week, whether some people are more likely than others to use them, and whether they provide different or better information than traditional surveys.
These insights will help determine whether these tools should be included in future clinical trials aimed at treating poor sleep in MS.
A person’s genetics can influence their risk of developing MS. However, few MS genes have been identified, and it is not well understood how genes drive MS development.
Previous research by Dr Nicholas Blackburn and his team into the genetics of MS families (families that have 3 or more close relatives who have MS) has shown that there are genetic changes in MS families that may affect a person’s genes in a way that contributes to MS. These changes are rare in the general population but can occur multiple times in a single family because of shared genetics. These changes might be why some families have many people with MS.
The focus of this current project is to increase the number of MS families studied to establish if similar genetic changes to those already identified occur across other MS families. Dr Blackburn and his team will then use the genetic changes identified in MS families to test whether the same genes are linked to MS in data from thousands of people with MS. Together, this will provide clues as to why MS develops so strongly in some families and lead us to better understand why MS develops overall, including in people who do not have a family history.
Myelin is a protective, fatty layer that surrounds nerve cells and supports their function. In MS, myelin is damaged, and the cells responsible for making it, called oligodendrocytes, decrease in both number and effectiveness. A promising approach to treating MS is to encourage remyelination, by stimulating immature cells, known as oligodendrocyte precursor cells, to develop into mature oligodendrocytes that can regenerate this protective layer.
Mr Jack McDonald’s research focuses on a protein called GPR17, a type of receptor found in immature oligodendrocyte cells that have the potential to become myelin-producing cells. This receptor plays a crucial role in helping these cells mature, making it a potential target for drugs that could promote myelin repair in MS. While evidence suggests GPR17 could be effective in promoting remyelination, we still don’t fully understand how it works or how drugs might act on it.
Mr McDonald is studying the pathways affected by drugs targeting GPR17 to learn more about how this receptor contributes to myelin repair. Using genetic tools, drug-based methods, and advanced cell models, he aims to clarify GPR17’s role in remyelination. By uncovering how GPR17 influences myelin formation, Mr McDonald hopes to inform future drug development, not only for GPR17 but also for other receptors involved in the repair of myelin in MS.
Multiple sclerosis (MS) is characterised by inflammation, loss of nerve protection (demyelination), and nerve cell damage (neurodegeneration). Currently, no treatment specifically reduces or reverses nerve-related disability in MS, representing a significant unmet need.
This project explores a potential new therapy using T-regulatory cells (Tregs), a type of immune cell. The research builds on previous findings showing that Tregs are replenished after autologous haematopoietic stem cell transplantation (AHSCT) in people with MS, a process believed to support long-term remission. Preliminary studies in laboratory models suggest Tregs may promote nerve repair, which this project aims to explore further.
Dr Malini Visweswaran and the team will examine whether Tregs from a person’s own cell transplant retain the ability to promote nerve repair, or if Tregs from people without MS might be more effective.
This research could pave the way for novel treatments targeting nerve repair to reduce disability in people with MS.
Extracellular vesicles (EVs) are particles with a lipid (fat) membrane that almost all types of cells release. EVs play an important role in travelling between cells as communicators and carrying a large range of substances that influence the biological functions of the receiving cells. EVs also have an effect on various disease processes.
EVs are hugely important in advancing our understanding of MS due to their role in communication between cells, their potential as non-invasive biomarkers (biological signs) and because they are able to cross the blood-brain barrier, a layer of cells that protects the brain from harmful substances. In MS, there is a great need to find reliable and non-invasive biomarkers and therapeutic targets.
PhD candidate Ms Drishya Mainali is travelling to Dr Magaña Setty’s laboratory at The Ohio State University for eight weeks to learn advanced techniques in isolating, characterising and analysing EVs. She will bring these techniques back to her laboratory at The University of Sydney, NSW and pass them on to her team. The techniques will also be used in ongoing research projects.
These advanced techniques are crucial for accurately profiling EVs in fluid samples from people living with MS. By enhancing her laboratory’s capabilities to profile EVs, Ms Mainali’s work will contribute to the early detection and monitoring of MS.
*For more details about the Ian Ballard Travel Award visit this page
