Astrocytes are characteristically star-shaped glial cells in the brain that perform various functions to support neuronal cells. While there has been extensive research into the function of neurons, progress in astrocyte research has been slower. Elucidating their role in health and disease may be key to unlocking new therapeutic targets.
The UK DRI at Edinburgh’s newest Group Leader, Dr Philip Hasel, joins the Centre from New York, where he completed a postdoc in Prof Shane Liddlelow’s lab. There, Dr Hasel discovered a distinct type of astrocyte that is only found in a single cell layer on the surface of the brain. In this Q&A, Dr Hasel explains what is so significant about these cells in disease, and why he has made them his research focus as he starts his lab at the UK DRI.
With Dr Philip Hasel
UK DRI at Edinburgh
What will your research programme focus on?
Understanding the role of astrocyte subtypes in brain function and dysfunction, with a focus on astrocytes that live at the border of the brain, in direct contact with a layer of protective membranes called the meninges. We found that these astrocytes are incredibly specific, expressing a gene not found in any other subtype of astrocyte, which allows them to be studied in isolation. My lab aims to understand the function of these cells, and what happens to them in disease.
What attracted you to the UK DRI?
In my research, I started asking fundamental questions about astrocyte biology and heterogeneity, and I discovered that they play critical roles in the context of neurodegeneration. What I found is that these astrocytes become super specialised and can show specialised responses to disease, for example, we showed that they undergo specific changes in response to amyloid plaque formation in Alzheimer’s.
It was clear to me that if we want to understand more about this, I needed to join an environment that is synergistic in answering these questions. The UK DRI at Edinburgh has incredible people when it comes to studying astrocyte biology in disease, and I think my programme will be a great addition.
Why is this an important area to explore? And what is the ultimate aim of your work?
What’s crazy, is that we know so much about subtypes of neurons. I bet every neuroscientist can name at least a couple of inhibitory neuronal subtypes. We also know that they occupy specific areas in the brain, and we've known that for a very long time. The field of astrocyte biology is running a little bit behind. We are now observing the exact same phenomenon: that astrocytes can specialise to circuits, and anatomical domains like the surface of the brain, or blood vessels.
This alludes nicely to them having specific responses in disease. And so I think there's a lot of value in understanding the subtype identities and what happens in disease, and finding out whether that's something we can manipulate. The goal would then be to exploit this new knowledge and leverage it into new therapeutic approaches.
What are you particularly excited about in your field at the moment?
I think that the current research into brain fibroblasts is super exciting. For example, take the cells that make up the pia mater, the layer that covers the brains surface. There is a lot we still don’t know about them, but they form a critical component in defending the brain against peripheral insults. As time moves on we have more and more tools at our disposal to study these cells, and maybe down the line it’s something I’ll work on as well, because I think it’s a super cool and underexplored topic.
Finally, what’s the most important thing you have learned from your academic career so far?
Identify a topic that is really important to you, that you’re eager and excited to learn more about. A question that you want to solve no matter what. Defining that is difficult, my advice would be to read lots of papers, go to meetings, talk to colleagues. Be courageous and make the big moves if you can: move country, change field, expose yourself to different opinions and expertise. And the second you find that key question or topic, nothing can stop you.
To find out more about Dr Philip Hasel's work, visit his UK DRI profile.
Article published: 18 April 2024
Banner image credit: Dr Melissa Cooper