Past the Bench: A dialog with Ethan Scott | Spectrum
Associate professor, University of Queensland
The scientists at Ethan Scott’s lab at the Queensland Brain Institute in Brisbane, Australia, come from a dozen different countries, including North Macedonia, Tahiti and the Seychelles. Her areas of expertise are just as diverse, extending to the areas of genetics, mathematics, computer science and optical physics. Together, the team spins what Scott calls an “expert network” to understand sensory problems that often occur in autistic people.
“We were really lucky with the people we attracted,” says Scott, associate professor of neuroscience at the University of Queensland. Scott is a transplant himself: he grew up in Newark, Delaware.
At the heart of Scott’s work is the zebrafish, a transparent tropical fish native to South Asia whose brain can be observed to an extent that no other vertebrate can – with the right tools. His team uses zebrafish autism models to study how sensory brain circuits can differ in people with autism. In search of the zebrafish’s neural secrets, Scott is ready to venture into unknown disciplines such as physics and mathematics. “I’m very excited to get novel results, and often this requires bringing new approaches into play,” he says.
Scott says he is also an advocate for social diversity and equality, especially when it comes to gender, and has worked with his university to develop more equitable recruitment practices. He told Spectrum about his feminist mother, streaming baseball games in the winter and a trick that makes stationary zebrafish “believe” they are spinning.
spectrum: What big question drives your research?
Ethan Scott: It is this: How do animals perceive the world around them and how do they react to it?
Now comes the fun part, where the “big question” breaks down into many smaller ones: How is information from different senses integrated? How does processing change in response to repeated stimuli? How does recent experience or context affect sensory processing? How are sensory networks changed in psychiatric illnesses?
S: How do you answer these questions?
IT IS: One of the challenges in examining sensory networks has always been that brain-wide functional imaging – such as functional magnetic resonance imaging – does not resolve individual neurons and targeted approaches such as electrophysiology cannot see the entire brain. Neither approach reveals sensory networks for what they are – large, diverse, and distributed populations of neurons.
Zebrafish are the only vertebrate model that allows whole-brain imaging of individual cells. Their larvae are also small, see-through, and develop outdoors. We have a system that allows us to see the entire brain with cellular resolution – tens of thousands of neurons at the same time.
S: What kind of system is that?
We recognize the calcium that is naturally released in active neurons. We do this by expressing fluorescent calcium-binding proteins in zebrafish neurons throughout the brain. The higher the calcium level in a cell, the more fluorescence we see and thus know which neurons are currently active. We detect the fluorescence signal with a so-called light sheet microscope.
Our light sheet microscopes, which we manufacture to customer specifications, deliver a thin layer of tightly focused light, each of which illuminates a level in the animal’s brain. If we move the light sheet and the focal plane very quickly, we can take pictures at different depths in a short time. This shows the activity of tens of thousands of neurons, sampled twice per second, throughout the brain.
We track this activity as zebrafish recognize and respond to sensory stimuli. Using various mathematical approaches, we then model how information flows through the system and how this information flow changes in genetic models of autism.
S: This work requires a lot of different skills. How did you collect that
IT IS: I was very fortunate to have great people in my lab with expertise from other areas. For example, Itia Favre-Bulle, a postdoc in my laboratory, is a trained optician physicist. She built our light sheet microscopes and shaped light into custom holograms to perform optogenetics – a way to artificially stimulate certain groups of neurons with light – in the intact zebrafish brain. For them, these were just pieces of the physics toolbox, but for us neuroscientists, it was magic.
Her coolest trick was to use the zebrafish larvae ear stones with “optical tweezers” – focused beams of light that exert force on the targeted objects – to trick the larvae into believing that they are rotating, even when they are they are stationary. Since the larvae were silent, we were able to put them under our light sheet microscope and describe the brain-wide vestibular network, which would have been impossible if we had actually rotated the animal. It was a creative and technical masterpiece for her and it was great fun to be part of it.
S: How does your work help people with autism?
IT IS: Many people in the spectrum have an atypical sensory processing – for example an acoustic hypersensitivity or problems combining information from two senses. We investigate sensory networks and the way the brains of animal models with autism process sensory stimuli differently than control animals.
For example, in 2020 we reported changes in auditory brain networks that appear to underlie auditory hypersensitivity in a zebrafish model of Fragile X syndrome. This suggests a possible mechanism for such hypersensitivity in Fragile X and autism.
S: How has the pandemic affected your work?
IT IS: It changed the way I approach running a laboratory. I always try to keep an eye on the wellbeing of my people, but during COVID-19 this has been my whole job. I have many international laboratory members who have been separated from their partners or families, and others who are supposed to come to us but are stuck abroad. Our sense of community and mutual support were crucial to staying afloat. It strengthened my view that a laboratory must first be a positive community and then a scientific team.
S: You are committed to the issues of justice and diversity. What are you doing and why
IT IS: I have worked on gender equality and diversity issues at my university and with the Australasian Neuroscience Society, particularly with a focus on gender equality. My particular niche has been job hunting, interviews and recruitment, which are full of practices developed by and for whites.
My mother is a retired professor and an influential feminist, and I think I grew up expecting women to be successful and in leadership positions. Growing up in this environment was good for my image of women, but maybe I was naive about how deep and pervasive the injustices of society are. Starting my own laboratory and caring for women – and working with colleagues struggling with institutional prejudice – made it clear to me how far we have to go, both institutionally and culturally. Raising two boys has also opened eyes to gender pressures and the expectations society places on children.
S: You grew up in the USA, then how did you get to Australia?
IT IS: My postdoc was in San Francisco, California, and my partner’s was in Santa Barbara, California, and that arrangement got pretty old after a few years. She got a great offer here as a laboratory manager and they have also come up with a laboratory manager position for me. With two tenure track offerings from a good university in a nice location, the Pacific Ocean seemed like a pretty small stumbling block.
S: What does a typical day look like for you?
IT IS: I usually go to school with my boys between the ages of 8 and 11 and bike to work from there. When I’m not teaching or in meetings, I either hide in my office, write scholarships or manuscripts, or browse the lab and talk to the team. Like many scientists, I live for the moment when new data is falling and we can make our first preliminary interpretations.
I work from home about once a week, and that’s good when I want to focus on something non-stop. My dog loves company too. The evening brings cooking, family dinner and bedtime stories for the boys.
S: What do you hear at work?
IT IS: When I do something that requires concentration, I can’t handle music with lyrics or a large dynamic range, so maybe just a bit of old choral music or solo piano or more often just quietly. If the job is easy and the timing is right, I’ll stream a radio broadcast of a San Francisco Giants game. They run in the middle of the day during the winter in Australia, which is pretty weird, but I’ve gotten used to it.
S: What are you doing for fun
IT IS: Having fun usually means finding ways to relax as a family. We started out with archery and we go shooting together once or twice a week. I’ve also enjoyed woodworking as a hobby since taking evening classes in woodworking as a postdoctoral fellow at San Francisco City College. The boys are reaching an age where I can get them involved in furniture making projects and it’s a great time.
In addition, we go outside whenever we can. We love to go for a walk on the beach with the whole crew or to hike in the rainforest. We are three season campers, but not what North Americans would expect; It’s nice here in winter, but too hot in summer.
S: How many unread emails are there in your inbox right now?
IT IS: Zero! I am scared of unread emails.