Multiple sclerosis (MS) is influenced by many common genetic variants, most of which lie in non-coding regions of the genome that regulate when and where genes are active - particularly in immune cells such as B cells. Understanding how these variants affect immune function is challenging, as each may have a small effect and their combined impact is difficult to study with existing tools.

This project will test how 100s of MS-associated variants influence gene activity and immune cell behaviour, individually and in combination. Using advanced CRISPR-based genome editing, high-throughput screening, and immune cell assays, it aims to reveal how genetic variation disrupts immune regulation. By mapping the pathways through which these variants contribute to MS, the study will establish a foundation for developing targeted therapies that address the underlying genetic drivers of disease, paving the way for more effective and personalised treatments.

Initial genome-wide association studies in MS identified hundreds of genetic markers linked to increased disease risk, raising hopes that these findings would reveal mechanisms that could be therapeutically targeted. However, for the past two decades, it has proven difficult to move from correlation to causation by determining how specific genetic variants alter immune cell function and drive disease.

Our research aims to fill this critical gap by systematically linking MS-associated genetic variants to their mechanistic target genes in B cells and therefore discovering molecular mechanisms underlying MS susceptibility. This knowledge will not only deepen our understanding of why some individuals develop MS but will also provide a stronger foundation for translational studies, enabling the rational design of new, more precise therapeutic strategies.

My background is in gene regulation, genomics, and human immunology, and my research has a focus on understanding how genetic variation influences immune cell function in health and disease. We recently completed a large study of autoimmune disease genetics that revealed new and unexpected pathways potentially involved in MS.

Given the ongoing challenges in the diagnosis and treatment of MS, I wanted to apply our technical and analytical expertise to try and help understand this devastating disease and provide new potential avenues to improve the lives of people living with MS.

In my opinion the increased evidence supporting a role for B lymphocytes in MS has been a major and impactful development in the field, with rituximab (a B cell-depleting therapy) holding significant promise as a therapeutic strategy. Related to this, the association of Epstein-Barr virus, a virus that is known to infect and alter B cell identity and function, is a compelling new area for MS research.

My favourite part of my job as a Laboratory Head at WEHI is training and mentoring the early career researchers in my team to develop their own scientific skills and thinking. Fostering scientific curiousity and creativity in how we tackle problems is very important, in my opinion, to find new ways to solve the big problems that we face in medical research.

Aside from technical difficulties that come with pushing current technological limits to answer important scientific questions, the major challenge that we face is the insufficiently resourced, unstable and disorganised funding environment here in Australia. The support from MS Australia is vital to help overcome this and allow us to focus on getting the research done to make discoveries and help patients.

I have been passionate about the natural world from a young age, and my first summer job when I was 14 was as a tour guide on Granite Island in South Australia, where I would guide people to see (at a distance) the small colony of Little Penguins based there. Sadly, the population of penguins on this island has deteriorated significantly over time, but this has a profound effect on my scientific development and curiosity about biology.