Professor Selina Wray is a Professor of Molecular Neuroscience at UCL Queen Square Institute of Neurology. Her lab focuses on understanding the molecular mechanisms of Alzheimer’s and dementia.
Can you tell us about your current research?
Our team is interested in understanding the very earliest changes happening in the brain cells (neurons) of people with dementia. The motivation for this being that for treatments to be effective, we believe we need to intervene in the disease process as early as possible.
To gain an understanding of early disease mechanisms, we are focused on rare, genetic forms of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) – in these individuals we know which faulty gene causes their dementia, whereas in the more common late onset forms the cause is likely to be a mixture of genetic and lifestyle factors.
We take a small skin biopsy from participants who carry these faulty genes, and use this to make stem cells. We can then turn the stem cells into the cell types affected in disease – so neurons as well as other cells called ‘glia’. These will contain the faulty gene that causes AD or FTD, and so we have a ‘dementia in a dish’ model that we can use to start to put together a timeline starting with the genetic fault, followed by the sequence of events leading to neuronal dysfunction and death.
What are some of the challenges in researching dementia?
AD and other forms of dementia are hugely complex diseases, and this means there are several challenges we face when it comes to research.
First of all, we don’t fully understand what causes the different forms of dementia – some people have rare genetic forms, but for others we don’t fully understand what the underlying disease drivers are.
As mentioned already, the inaccessibility of the brain during life means we rely on models that we can grow in the lab to study the cell biology of disease – but no model is perfect. For example, our neurons are human but they lack the structure and diversity of cell types in the brain. On the other hand, for researchers who use rodent models, they have an intact organism but the size and complexity of the brain is lower than that of a human.
So, we need to use all these tools to piece together the dementia jigsaw, as well as take advantage of technology advances to develop new and improved models.
We are entering a new era of dementia research where we are starting to see successful clinical trials emerging. But treating AD and other dementia will also be complex, because of the need to get treatments into the brain (which is protected by the blood brain barrier) and also the long pre-clinical period of disease – by the time someone has symptoms, it’s likely that changes have been happening in their brain for several decades.
So as well as the pre-clinical work we do, I’m also excited by progress to develop ways to diagnose earlier and more accurately, so that we can treat as early as possible.
How can stem cell technologies help us better understand neurodegenerative conditions like dementia?
One of the big challenges in dementia research is that we can’t access the human brain during life, and so using stem cells to model dementia is the only way we can have an unlimited supply of human brain cells to study in the lab.
Can you tell us about the ‘Brains in a Dish’ project?
In addition to our laboratory science, we are also committed to communicating our research widely, to patients, families, policy makers, fundraisers and students who will become the neuroscientists of the future!
The Brains in a Dish project was led by my friend and collaborator Charlie Murphy, who is an amazing artist and made a series of artworks, installations and workshops in response to the research we do in the lab.
At the end of 2022, we had an amazing opportunity to hold an exhibition of this work at the Cooper Gallery in Barnsley (my hometown!) and I was so excited to showcase some of the work we do there and reach audiences we wouldn’t normally reach via our London-based engagement projects.
UCL is building a new centre for excellence for neuroscience that will bring academics, clinicians and patients under one roof. Can you tell us more about the project and the benefits of the new building?
We will move into the new translational neuroscience building at the end of the 2024. It will really change our research in multiple ways.
Our current facilities are quite old and not purpose-built for the work we are doing, so to be in state-of-the-art new facilities will accelerate our work as well as enabling more collaboration, because it will bring together scientists from across multiple sites under one roof.
This will increase those chance “corridor conversations” that happen which can turn into exciting new projects!
Further, we will have scientists, clinicians and patients all in one building. Our work relies on collaboration with clinical colleagues and samples that are generously donated by research participants. And nothing keeps you focussed on the goal of developing treatments like sharing an entrance to a building with people living on the disease you are working on – it’s a good reminder of our mission.
What working achievement are you most proud of?
This is a tough one – I really enjoy seeing students and postdocs in the lab grow into independent researchers and drive their projects forward with such enthusiasm. But as our research relies on samples from research participants, I would have to say I’m most proud of the work we have done to share our findings with the patient community, such as speaking at the rare dementia support groups.
People help our research projects selflessly, and I really enjoy being able to communicate our research findings back to them and see them get excited about research!
Why would you recommend UCL as a place to study neuroscience?
The neuroscience community here is huge and spans all aspects of neuroscience, from the translational work we do to really fundamental studies into how the brain works. Even after 10 years at UCL, I hear about fascinating work going on across campus that I hadn’t come across before, and it is amazing to be part of the neuroscience community.