I actually started my research career in an entirely different field, studying the molecular mechanism of sex determination in birds. It was only later in my career, during my time in Martin Raff's lab in London, that I developed an interest in the oligodendrocyte - the cell type damaged in MS.

I spent five years working in London, where I was introduced to the oligodendrocyte, and have been working with this cell ever since. Oligodendrocytes are the cells which produce myelin, the protective cover on nerves and the main target of damage in multiple sclerosis (MS). It was therefore natural to progress from a love for these cells to an interest in understanding how they are damaged in MS, and how we might protect them from damage and even promote repair.

The finding that myelin repair occurs naturally in the brain was a crucial step in giving researchers confidence that it would be possible to develop therapies that can repair the damage that occurs in MS lesions. Although the natural repair response in the human brain fails over time, MS researchers all over the world have made great progress in understanding the molecules and mechanisms involved in myelin repair and have begun to develop strategies and new therapies to promote repair. The discovery that brain-resident immune cells (microglia) can promote myelination opens an entirely new avenue for developing therapies to promote remyelination.

Most MS therapies treat the inflammation and reduce symptoms in the early stages of MS. However, no current therapy averts the risk of entering the progressive phase of MS - which is characterised by the ongoing degeneration of myelin and an unavoidable decline in functioning. The lack of therapies that target the progressive phase of MS is a significant unmet need in the field. One approach to treat progressive MS is to enhance myelin repair, thereby promoting functional recovery and limiting the propensity for otherwise demyelinated nerves to degenerate.

Microglia are a type of immune cell found exclusively within the brain and spinal cord. We have recently identified that some microglia, which express a protein on their cell surface called MERTK, influence the generation of the myelin-producing cells of the central nervous system (CNS). This finding provides an opportunity to develop new therapies to promote myelin repair.

We hypothesise that microglia that express MERTK, or the factors produced by these microglia can be used to improve remyelination.

There is compelling data to show that microglia that express MERTK can promote myelin repair and provide an excellent opportunity to develop new therapeutics and therapeutic strategies. This project is directed towards identifying ways in which we can capitalise on this opportunity and includes both medium-term and long-terms aspects. In the medium-term, our establishment of a method to increase the proportion of MERTK-expressing microglia and confirmation of their benefit during myelin damage and repair using dexamethasone could provide a clear path to rapid translation to the clinic, given that dexamethasone is already an FDA-approved drug. An early-phase clinical trial is possible within five years.

In the longer term, our identification of the myelin-promoting factor secreted by Mertk-expressing microglia will provide an opportunity to develop a new remyelination-promoting therapy. Enhanced myelin repair is also likely to reduce the likelihood of future attacks in these areas of the brain and spinal cord. All this will serve to reduce existing disability as well as minimise the chance of future disability.

I love the discovery aspect of working in the lab; our job in science is to develop new knowledge, which means that when you get a new result you may be the very first person in the world to know something. Of course, many of the problems we work on are very challenging, and answering the questions we are asking can involve developing new techniques or adapting old techniques in novel ways. This usually involves multiple failures, and can take months or years of work, so in science we always have to be ready to play the long game.