UNC Health Talk

Tracing the Development of Neurons

By Matt Englund, PhD

Growing up in Elkin, a little town between Winston-Salem and Boone, Stephanie Gupton, PhD, assistant professor of cell biology and physiology, was fascinated by the self-sufficiency of plants, an interest that led her to study biology.

Today, she works to understand how neurons change shape – a key process during early brain development. Her research recently earned her a Jefferson-Pilot Fellowship Award, which is given annually to promising junior faculty at the UNC School of Medicine to explore new ideas in research, teaching or clinical treatment. We sat down with Gupton for a Five Questions feature to learn more about how she came to UNC, how her curiosity drives her research pursuits, and the role mentoring plays in her lab.

What got you interested in science?

I first got interested in science growing up. It began outside, gardening and wandering around in the woods. I remember being amazed at how plants can make their own food. So I did my undergrad in botany because I was enamored of how independent plants were. All they needed was sunlight to make food.

When I was an undergrad I went to NC State and did research in Nina Strömgren Allen’s lab. She was one of the founders of video microscopy. She and her husband were the first to put a video camera on a DIC [differential interference contrast] microscope that allowed them to watch organelles moving inside cells. I worked in her lab looking at how the endoplasmic reticulum reorganized in tobacco cells during cell division.

Just watching these cells, I fell in love with cell biology and learning about the smaller parts that move within the cell.

I did my graduate work with Clare Waterman at Scripps Research Institute. I continued to use high resolution microscopsy to look at the cytoskeleton in migrating epithelial cells, in a wound healing response. Those were animal cells, which got me interested in how cells move, and the cytoskeleton that powers that.

The cytoskeleton is composed of a network of polymers in the cell that give the cell structure. That’s why they’re called the skeleton, but it’s a bit of a misnomer because they polymerize and depolymerize so the cytoskeleton is dynamic structure that helps cells move and remodel.

How did you get started working on neurons?

My work at Scripps got me interested in taking the expertise I had accumulated in microscopy and the cytoskeleton and applying it to studying how neurons change shape throughout their development, which I started working on as a postdoctoral researcher in Frank Gertler’s lab at MIT. Interestingly the cytoskeletal rearrangements that make cells move also power neuronal development.

Neurons start out as spherical, symmetrical cells, and during development, they morph into highly elongated, polarized cells with long extensions, which don’t look like any other cell type in your body, and that unique morphology underlies their unique physiology. The extensions eventually reach and innervate appropriate synaptic partners to establish the functional neural networks of the brain.

If they don’t make the right connections, the neural circuits and the behaviors they encode may be compromised, resulting in mental and neurologic disorders. While my research isn’t focused on a particular disease, and rather grows out of my own curiosity about how neurons work, the fundamental knowledge we gain may play a part in understanding how the brain works, what goes wrong in certain disease states, and maybe someday how to ameliorate those problems.

What brought you back to North Carolina and why choose UNC in particular?

UNC has long been a Mecca for microscopists that study the cytoskeleton as well as for a range of neurosciences. There is a long list of awesome labs here that do that, which really tied in with my interests.

The cytoskeletal community, the microscopy community, and the strong neuroscience community made this a destination for me. Coming to UNC was an opportunity to learn more hardcore neuroscience just by being here, and apply my cell biological skills to neurons.

A lot of what we do in my lab is live cell microscopy. It’s one of the workhorses of our lab—looking at subcellular organelles and structures in a developing neuron. When you mess those up, what does that do to the shape and function of the neuron?

Where do you hope your research leads?

I want to understand how neurons work. I’m interested in how the cell functions. There are plenty of “eureka” moments along the way, but there’s not going to be a moment when I can say “I’m done.” We want to learn how the cell changes and adapts in response to its environment, age, and genetic make-up, and I think we’re going to keep discovering new paradigms continually.

When a neuron goes from being this small symmetrical cell to this highly elongated cell, you need both changes in the cytoskeleton to push the cell into that long shape, but also an increase in the surface area of the neurons. It needs to be adding surface material, new plasma membrane material, to the outside of the neuron as the cytoskeleton changes the shape of the plasma membrane. And so what we are interested in is how neurons are able to accomplish those changes in a coordinated fashion.

Because if the cytoskeleton pushes out, but it doesn’t have membrane material to push out then that’s not going to work, it’s not going to be able to move. And if the cell has the plasma membrane material but doesn’t have anything to force it to change shape, then that’s not going to work either. You need both of them to happen at the same time.

We study enzymes that are enriched in the brain that regulate both of these discrete cell biological pathways in order to figure out how the neuron is able to change shape at the right place and at the right time.

In addition to the Jefferson Pilot Fellowship, you were also recently awarded an Outstanding Mentor Award by the UNC Office of Postdoctoral Affairs. What role does mentoring play in your lab?

I always tell my lab members that I’m invested in their success for them, but that my success is also directly linked to their success, and vice versa. I think that’s what turns a group of researchers with different interest and areas of expertise into a good team: when they know that they all need each other to do well.

I like to have meetings with the whole lab where people show their good data and their bad data, the ugly data, and there is a lot of conversation about how to how to improve experimental procedures, what are different approaches to a particularly difficult problem. It gives all of us a chance to talk about what is working and what isn’t, and how to fix it. It’s a process that helps us learn from and mentor each other.

One of the other exciting parts about having a lab at UNC is getting to mentor both cell biologists and neuroscientists in my lab. The diversity of our expertise and interests has helped our lab to understand the cell biology of neurons in a way that is unique. It creates a niche for our lab.

The most important thing is finding people that are self-motivated and driven, and creating an environment for them to excel at what they are good at. But they also need to feel comfortable enough to take some risks, try to learn and do new things. That’s what helps researchers and science grow.