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One on one with...Nicola Allen

Nicola Allen

Nicola Allen is a neuroscientist, but she doesn’t focus on the superstar of the brain, the neuron. Rather, she studies astrocytes, star-shaped cells once thought to be “filler,” but recently shown to be crucial to brain function–the producer, director, stage designer and supporting cast to the neurons.

These mysterious brain cells have only recently edged into the field of neurobiology as a viable research area and they have significant potential for helping to understand neurodevelopmental and degenerative diseases like autism, epilepsy, schizophrenia, stroke and Alzheimer’s disease. These prolific cells are, Allen says, a major player in the brain, despite their longtime obscurity.

Named for their multi-armed shapes–where long branches extend from a single cell body to touch over 100,000 neural connections known as synapses–astrocytes do more than provide the support system and scaffolding for the brain. While the bushy astrocytes don’t transmit electrical signals of their own, they use chemical signaling to affect nearby neurons, setting the stage for complex neural messaging. And, like neurons, astrocytes exist in a variety of forms found in different configurations throughout animals’ brains, increasing in number roughly proportional to the brain’s size.

To better untangle the role of these enigmatic cells, Allen’s lab investigates astrocyte protein families that appear to be crucial in neural development, operation and adaptation.

What drew you to start researching the brain?

Growing up, my all-girls’ grammar school in England had great biology classes and teachers. I thought I’d be a vet or a doctor, but I realized that fundamental research drew me the most because you’re finding out what’s really going on, whereas in medicine, you’re at the end phase of new discoveries. The brain is the most mysterious of all the organs, so I wanted to learn more.

I was the first in my immediate family to receive a PhD, which focused on the cellular mechanisms that go wrong during stroke. Neurodegenerative diseases interested me the most because they are so enigmatic. My mom’s always telling me to hurry up and cure Alzheimer’s–hopefully, our findings will help lead to that someday.

Why are astrocytes overlooked in conventional neurobiology?

Cell types like astrocytes are understudied even though they have huge implications for quality of life and aging. Traditionally, researchers thought that studying neurons would tell us what we need to know about the brain because they are the cells that are sending electric signals, making decisions and relaying messages. Now, we think that astrocytes are just as useful to study–not only do they make up about 50 percent of the brain, but they are actively instructing the neurons on how to connect with each other as the brain develops. And in adult brains, astrocytes are modulating ongoing neuronal activity, which will completely change the output of the neurons. Astrocytes are involved in every stage of development and likely have different roles as one ages, so they are incredibly important.

What are the implications for astrocytes in disease?

Other researchers have done experiments in the last few years showing that, in mice with genetic predispositions to developmental disorders that model autism, the introduction of astrocytes actually rescues the defective neurons. New astrocytes don’t completely cure the mice, but their presence increased the growth of neurons’ branched projections and alleviated a lot of symptoms, such as breathing difficulties.

Similarly, introducing mutant astrocytes to normal neurons is enough to make the neurons defective. So there is this real, constant interaction between cell types that is setting up the right connections in the brain and the number of connections.

So could a better understanding of astrocytes lead to “new and improved” brains?

The long-term goal of studying astrocytes is to learn how to repair damaged circuits by prompting neurons to reform synapses in a controlled way. By reintroducing astrocyte factors to a damaged brain, you could, in theory, encourage neurons to create new connections and improve brain function.

Previous work showed that bringing astrocytes from young animals into old animals gave the old animals a new plasticity in the brain– that is, they were more easily able to make connections that improve cognition–while bringing in old astrocytes had no effect. Studies done in 2013 found that introducing human astrocytes into mice resulted in an enhanced ability in behavioral learning in the mice, potentially because the larger, human astrocytes could interface with more synapses.

We want to understand these special features of young astrocytes that enable the brain to be flexible and create new connections. However, in eventual therapeutic applications, you wouldn’t want to introduce too much plasticity, or the brain would forget everything it learned instantly. We want to manipulate those features in a controlled way.

From left to right: Catriona Lewis, Isabella Farhy, Matthew Boisvert, Nicola Allen, Tongfei Liu, Cari Dowling

What are the big questions your relatively new lab at the Salk Institute aims to tackle?

Astrocytes secrete many proteins that affect synapses. Before I began my research, it was already known that one class of proteins the astrocytes secrete establishes normally structured synapses between neurons. However, those synapses were silent–they didn’t have any electrical activity. I discovered a second class of proteins that is responsible for affecting the ability of the neuron to respond to neurotransmitters and communicate with its neighbors. This isn’t the whole story–this class only establishes an immature connection between neurons–so we are looking for an additional class of proteins that strengthens synapses later in mature brains. We also know that astrocytes secrete classes of proteins that make inhibitory connections between neurons, but we don’t know what these proteins are yet.

There are a lot of myths about the brain. Which, as a neurobiologist, would you most like to dispel?

The myth that we only use 10 or 20 percent of our brains still persists in culture even though it’s been discredited. In truth, nearly all of our brain areas are active at some time over a given day.

What advice do you convey to new scientists?

I think the most important thing for a scientist is a sense of perseverance and, along with that, a positive attitude. Also, being open to new ideas is crucial. Even though science is about being inquisitive, sometimes it’s easy to get stuck in one way of thinking. Scientists should be receptive to new ideas, able to look at findings and follow up across disciplines if needed.

That is what’s great about the Salk Institute. I believe very strongly in the mission of the Institute in that we’re doing research to understand basic biology, but in the long term this research will likely have a tangible effect for people. So much of what we study has the strong potential for therapy. Having the flexibility to follow questions and develop collaborations will help us reach that knowledge faster.

What would people be most surprised to find out about you?

I spent six months traveling before doing my PhD, backpacking through Fiji, New Zealand, Australia, Indonesia, Singapore, Malaysia and Thailand. While in New Zealand, I went skydiving, which was fantastic. After that I did another backpacking trip with my brother to Vietnam and China for two months. I’ve been scuba diving in Malaysia, Thailand and Vietnam. Next, I’d love to go to the Galápagos Islands.

What do you do in the little free time you have between setting up a lab and research?

My boyfriend and I kayak, snorkel, watch wildlife and frequently visit the San Diego Zoo. If I really need a break, I watch British crime series, particularly PBS Masterpiece Mystery: Inspector Lewis, Prime Suspect, Sherlock and others.