Return to the audio for How to Science Episode 5, with scientist Sara Aton.

 

Monica Dus: I am Monica Dus. I’m a professor at the department of Molecular, Cellular, and Developmental Biology.

Sara Aton: My name’s Sara Aton. I’m also a faculty member in Molecular, Cellular, and Developmental Biology, and I’m happy to be here.

This podcast is really about understanding what’s your science story and about your research and what makes you tick when you do science. Why don’t you tell us a little about what is your science story? How did you get to where you are today?

SA: Oh my goodness, it was a meandering path, I’ll put it that way.

I didn’t know that I wanted to do science as my forever job until I was well into undergrad. I started out at a community college, and in fact, my initial plan was to go to one of these very expensive, elite art schools, to the point where in high school, I was preparing my portfolio.

The fact that I was a woman really helped me get into college. Because if I had been a man in my family, the expectation would have been that I would’ve gone to trade school, and I would have been a plumber, basically, just like my dad and my grandpa and his dad. The fact that I was a girl–I think my dad was just like, “Well, I don’t know what to do with this.” But what are you gonna do? “You gotta learn something, otherwise you’re just gonna be living with me forever.”

I think there was that aspect to it, where the fact that I was a girl actually was hugely beneficial in terms of him psychologically being like, “Yeah, you should go to college. That’s a good idea to go to college.” I think if I had been a guy, and I’d said I wanted to go to art school, he would have kicked me out of the house. There wouldn’t have even been a discussion. He would have been like, “You’re crazy. We’re gonna go get you medication.”

Nobody in my family had gone to college. So I put my portfolio together, and for a couple years in high school, I was working toward that, thinking I’ll either sink or swim with this. Either I’ll go and be a great artist, or I won’t. These schools are not inexpensive. I realized that, unless I was given some amazing scholarship, there was no way. My family and I couldn’t make funds appear out of nowhere.

And then meanwhile, I had taken the SAT and ACT, and based on those scores alone, I was given a full-ride scholarship with enough funds over and above tuition for the local community college. So the decision was either I would go to art school and, through some means that were absolutely unknown to me, I would find the funds to get through that. Or I would do “art school” (in air quotes) at my local community college, and I would get a Bachelor of Fine Arts and a Master of Fine Arts there, and do that with essentially a full ride scholarship, and enough support that technically, if I didn’t want to work, I wouldn’t have to. My housing and room and board would be paid for by the state.

So I decided to go that route, and it wound up being the best decision of my life. Because once I got started there doing what I intended to be–a double major in art and psychology–I realized I hated the idea of being an artist and having my survival depend on that. So something I truly loved as a process that I went through on my own, I absolutely hated doing it as a student. I hated working for grades and working for the approval of my peers.

And looking down the road at what lay ahead, and seeing how the students who got their Master of Fine Arts then went on to struggle–looking down that road about a year or two into community college, I realized, “This is a terrible idea. I will not be happy.” At that point, I was already unhappy and I thought, “Oh my goodness. This is the rest of my life, and there's a 99-percent probability that I’m not going to succeed.”

I told you; this is a very meandering story!

So around the same time–as I said, I was double-majoring in art and psychology–I took a job as a housing assistant to adolescents and young adults who lived in this group home and had autism. I was working rotating shifts, so I would have overnight shifts with the kids, helping them get ready for school in the mornings...

And these were elementary and middle school and high school kids?

SA: Just a couple years younger than me.

Getting to know these kids and getting to see that there was a really different way of seeing the world through their eyes, and also seeing the things that they struggled with, really convinced me that what I wanted to do was know more about the brain. That was something that not only was a career path that I thought I could handle–in terms of mentally and emotionally handle. But it was something that I thought, “As a human being, I need to do this. I need to basically make a contribution to knowledge.”

That’s really fascinating, because you really became interested in the brain through the reality of mental illness, right? Rather than just reading about it in books. So it was rather poignant, especially since they were your own age, and you could see what it was like for you and for them, right?

SA: That’s right. And I have to say, my experiences with them changed my perspective on even how my own brain works. I probably would never have had an appreciation for it at that particular age, otherwise. So that is what drove me to know more about the brain.

And being in a small community college setting, there wasn’t a lot of research going on. So what I did at that point was look around. And I didn’t know. I wasn’t savvy to the world of research–to academia, generally. I basically had friends of friends who were at the University of Michigan, and I did a little bit of very early internet research. You know, because the internet was kind of a new thing! And I realized that Michigan is one of the top places in the world for behavioral neuroscience research.

The only thing I really understood at that point was that research is a process that brings new knowledge into the world, and basically that all of the stuff I had read in textbooks came about through years and years of research. And at that point in my life, I really had almost an existential yearning to make some sort of contribution to science that would outlive me. That was major driver of turning to the world of research.

So I came to the University of Michigan. I transferred after my second year.

How was it going from a community college to Michigan? How did you find a lab? How did you go about doing research at Michigan?

SA: I spent a lot of time lost here; I’m not gonna lie. I was lost in many respects.

I was coming from a more rural environment to Ann Arbor, which–believe it or not–Ann Arbor seemed like this incredibly cosmopolitan place with one-way streets. It seemed incredibly cosmopolitan to me. So culturally, I felt a little bit lost, and I most certainly didn’t really know what scientists even were, or looked like.

So I was out of my element in a few ways, but again, thanks to this new thing called the internet, I was able within a few days after arriving with my truck and all my stuff to Ann Arbor, I was able to get online and start to navigate the university website. There was this HR portal that had links to jobs at the medical school doing research. I wound up working in the lab of Dr. Sue O’Shea, who is still here. And that was my first research experience. And that is what really got me started.

Dr. O’Shea was a great research mentor, but she was also a great career academic mentor for me, because again, I was really lost, and she was like, “You need to take your GRE, you need to think about which graduate schools you want to apply to.” She was very, very encouraging and talked to me about things that were gonna happen to me way down the road. So she very nonchalantly talked to me about, “Oh, when you have your own lab, this is what you’re going to encounter. This is the process for writing grants. This is what the tenure track is like.”

That confidence that she exuded toward me was huge, because I felt very out of my depth, and having somebody say, “You’re gonna make it! Here’s what you’ve got to do, because you’re gonna make it!” was incredible. So I have to give a shout-out to her.

That must be an amazing experience–to have somebody that really believes in you and gives you confidence.

SA: Yeah, who says, “You’re gonna be a scientist. You are a scientist, and you will stay a scientist.”

Because it was clear to me very early on that it wasn’t trivial. Getting your grant funded wasn’t just a matter of course. Getting through the tenure process wasn’t something that just everybody did.

Your first day in the lab: What was it like? The first time you held a pipette...

SA: I was thinking that I’ve worked with people who are coping with developmental disorders, who aren’t typically developing, and now I’m going to do research that is about early nervous system development. And I thought this has the potential to be so relevant. Now, what I actually did in lab, in retrospect, was a small piece of a piece of a piece.

As science is, right?

SA: As science is. But I had just this incredible hopefulness about working in a laboratory setting, which is how people learn new stuff. That, to me, was just completely mind-blowing. I have to say, I was probably a little bit starstruck like that. For the first few weeks, just walking in there, it was just like, “Wow!” It was sort of this magical feeling of Cinderella going to the ball. It was like, “Wow, I’m really here, and I’m doing science.”

Only instead of the crystal shoe, you have a pipette.

SA: Right; instead of a ball gown, I had a lab coat.

That’s right!

SA: And gloves.

So was it a defining moment when you were an undergrad and you were doing research? Or was there another defining moment that told you that was the right decision? Did you ever consider medical school? Or that was it: You wanted to be a scientist?

SA: I knew I wanted to do a Ph.D., but the one debate I had was whether I wanted to do a combined degree and do an M.D.-Ph.D.

And I think the appeal was twofold. The first part of the appeal was that I thought it would open doors for me to be able to do translational research, which particularly early on as an undergrad, I thought, “I want to do this.” I was thinking big. I was like, “I wanna fix debilitating neurodevelopmental disorders.”

Thinking back to the people that you worked with.

SA: Yeah, so I thought of course I wanted to be able to translate. And by having an M.D., that would be a great way to help me translate. I was also just very, very greedy for knowledge and information and education. Once I got a little taste, I just wanted more and more.

It’s very addictive.

SA: It’s very addictive! And at the time, I was looking other students facing this huge future financial burden, which is their students loans for medical school.

And time commitment, right?

SA: And time commitment. But I wasn’t thinking about the time. I was only thinking about the money. I was like, “You know what, I can get all of that education for free, and it’s a bargain. I don’t have to pay for med school. It’ll be part of my combined degree.”

And I’ll never forget: I was part of a student organization for undergrads who were interested in neuroscience research, and we had as a guest speaker at one of our meetings, Rich Hume, who is in our department. He’s very involved in the neuroscience community. And he was speaking to us about how to prepare for graduate school.

And I raised the question, “I’m struggling with this: Should I do a combined degree, or should I just do a Ph.D.?” And he said, “Well, it’s very simple. Do you see yourself enjoying doing clinical work? If so, do the combined degree.” And people who know me know that I probably would have a lousy bedside manner. I would be great as like a brain in a jar somewhere. And I thought about it for maybe two seconds, and I was like, “Of course I don’t want to do clinical work!” And that was it. He actually put it to me so simply and I was like, “Okay, of course. I just wanna do research. That’s all I really care about.” So of course, I just went the Ph.D. route.

There were numerous questions that the lab was going to be addressing, but one of the ones that struck me early on was how neurons in the central clock of the brain communicate with one another to coordinate their timing together. So at the time, the question was: You have all of these neurons in this very small nucleus that you need in order to have daily rhythms of behavior.

And at the time, people thought that each and every one of those cells has a clock and a firing rhythm, but they don’t have the same speed of timekeeping–some run slow, some run fast. And the idea was that there has to be some mechanism by which they communicate with one another in order to coordinate their timing, so that the animal has one clock instead of hundreds or thousands of rhythms that are going on simultaneously.

And to me that was such a fascinating and actually very open-ended, but such a fascinating question of network communication. And I became so in love with that question that I forgot all about neurodevelopment, really. But everything was ahead of us, and I think that could be terrifying, but I was very excited by that.

I feel that’s a really central part to science–that we work really hard, we have long hours, and there’s so much disappointment pretty often, but that somehow every morning, we go to lab and we are so in love, or maybe addicted, or both, to what we do. So, what makes you tick? Is there one thing that you can point to?

SA: I love mysteries. I love surprises. And I think there really aren’t that many jobs where, walking into work in the morning, you really don’t know what the day is going to bring you. And I think that’s the thing that I love most about this job: Every day I walk in, and I don’t know what’s going to be going through my mind when I walk out, because I have no idea what could come out of nowhere and blow me away.

So what I study now is sleep and what sleep does for the brain. And I think part of the reason why I’m drawn to that is it’s completely mysterious. We don’t know a lot about it.

We have to sleep. We cannot not sleep. Why is that?

SA: We all have to sleep! And we don’t know why.

It’s really one of the most fundamental unsolved mysteries of all biology, right? Because we know that even organisms that we usually think aren’t sleeping because they don’t close their eyelids–worms and fruit flies–they all sleep.

SA: Yeah, it’s amazing. And you know, the funny thing is that from early days, everyone thought, “Maybe mammals do it, but reptiles really don’t. Or maybe vertebrates do it, but surely invertebrates don’t.” And I think the more we look, the more we realize how conserved this is.

So a great example is migrating birds. Birds that migrate over long distances will be in flight for days and days and weeks at a time. They’re going across oceans, so there’s no place for them to stop and land, and you would think they’re not sleeping that entire time.

And it turns out that if you instrument those long-distance migrating birds and look at what’s going on in their brain, they do catch naps. They catch naps while they’re coasting and while they’re banking. They will actually have unihemispheric sleep, which means that they will sleep with one side of their brain and not the other, and they will catch sleep in this amazing circumstance, where you would think there’s no way they could be fast asleep flying through the air. But they are! At least half of their brain is sleeping from time to time.

See, that’s what I find truly fascinating about science is that, to me, it’s like an unending pervasive source of beauty. You know, like half of their brain sleeps as they’re migrating?! But nature has such a beautiful way to find a solution that works, right? Randomly, through trial and error, it finds this mind-blowing solution to things.

SA: Yeah, and I think the one thing that’s beautiful about science generally is that all you have to do is look, or know how to look, or have the tools to look at what’s going on in a new way. And in biology, there’s this endless source of wonder. You know, it’s just marvelous the things that nature has done.

And it turns out that if you look across species–if you prevent their sleeping for long enough–invariably, the animals will die. So there’s something going on there.

I think that if you look at what nature does, just by itself, it’s actually just endlessly interesting and wonderful.

Yeah, I don’t think it’s ever ceased to surprise and inspire me in all the years I’ve done science. I think there are very few things that are like that, and one thing I get upset about is that many times when we communicate to the public, we tell them, “My research is useful because of this.” But we really fail to tell people why we love doing what we do so much–that it’s intoxicating.

SA: Yeah, and I think those are two totally different things. I mean, I think what drove me into science is the utility. It was really about making something out of my life that was for other people to use after I was gone. It was totally utilitarian.

But what keeps me in it is the magical feeling that you get if you’re seeing something, and you realize you’re the first person seeing this for the very first time. I’m actually getting shivers thinking about it, but it’s so exciting. And I think that’s why we do it. Because there are long hours, and people don’t do it for the money, despite what people might say testifying to Congress. We are not in this for the money.

The utility: It’s really important, because obviously we want to understand how nature works, so we can fix a lot of things that don’t work, but there’s also this other deeply personal part of science–that the way you do science is different than anybody else. It’s like your favorite color or ice cream flavor. And sometimes I think we fail to tell people. For instance, I think a lot of science is actually very similar to art. What do you think, being an artist?

SA: Yeah, I absolutely do. The data are what they are. So the reality of the world is what it is, but your way of seeing it and sort of carving out the obstacles that are in your way to actually seeing what’s going on–everybody has a different strategy for that. It’s hard to teach the actual process, because everybody’s process is different, and I think it’s hard to explain to people that everybody solves their research puzzles differently. They have a different approach. There’s something very creative in that. I think about it a lot. You’re sort of carving away and revealing what’s underneath, and ultimately what’s underneath is what it is, but the way that you do that carving is uniquely your own.

You’ll never get two scientists to approach the same question with the same strategy. And that, to me, is actually really fun.

Can you tell us a little bit more about what your lab is studying?

SA: We study what sleep does with regard to how neurons in the brain process information differently, based on new learning experiences, looking at different types of learning that depend on different circuits in the mammalian brain.

We’re looking at the type of memory that we think of when we think about our own personal histories and things that have happened to us. We’re also looking at very early information processing in the visual system, based on prior visual experience. And in both cases, there is a change in the brain that’s occurring over a period of hours. It turns out that in both cases, those changes are dependent on sleep.

And what we would like to know is: Why? Why are these changes occurring, specifically during sleep? And why do they not seem to happen if you prevent the animal from sleeping?

So what happens during sleep?

SA: With regard to memory, it seems to be promoting the long-term crystallization of memory. And with regard to the visual system, it seems to be causing changes in the way that neurons process a specific type of visual information to make that process seem more efficient, based on having seen that sort of information previously.

It’s very analogous to if you were looking at, maybe for example, word finds.

That’s like where there’s a bunch of letters and you have to find “ice cream” in there?

SA: Exactly. And you’re looking for actual words to pop out. If you do those all the time, they actually become easier for you to do; the words just pop right out at you. This is basically something analogous that we can study at a very low level in mice.

And so in both cases sleep seems to be contributing, but as I say, we don’t know why. And the reason we don’t know why is that when you go to sleep, there are so many variables that are changing simultaneously in your brain. The pattern of activity in individual neurons, and brain circuits as a whole, is changing very dramatically. There’s changes in neurotransmitters and neuromodulators that are being released in the brain. There are changes in your brain temperature. There are changes in gene transcription and protein translation. There are even changes in how metabolites flow across the space between neurons in the brain.

So there are all these things that are changing simultaneously, and for a hundred years now, people have been doing the experiment of preventing animals or people from sleeping. The problem is, if you do that, you’re changing all of those things. So assigning causality has been really really difficult.

Fortunately, in the past decade, there have been all these advances which make it very easy to manipulate one feature of all of those, which is the pattern of activity in particular circuits in the brain. And we use those tools–we basically use tools that other people have developed from years and years of their own research that allow us to go into the brain while it sleeps and introduce a pattern of activity that looks more like wakefulness. So the animal is sleeping, and many of those other changes are going on as they normally would, but the activity pattern is changing. So what we’re really studying is, What is the significance of the pattern of activity?

Yeah, you can make an analogy: Before, if you would wake up the animal and stress them (well, prevent them from falling asleep), then imagine a person that’s sleeping. The lights are off, and it’s really quiet, and you start playing the drums or something, and you turn the lights on. But now, most of it is the same. What you’re doing is a very specific change in just a small neural population–just a few cells–and it’s maybe like having your faucet or your clock just go “tick tick.” So it’s just a very small change. The lights are still off, and it’s quiet, and so you now test: What exactly is this “faucet,” or this neural population, doing to help?

SA: Right. It’s a slightly more subtle manipulation.

Being able to go in and modify one of those variables instead of modifying them all at the same time is basically allowing us to ask different questions than we could previously about what is it about what’s going on the brain while we’re sleeping that is useful for different processes that seem to be going on.

And your lab uses ways to listen to the whispers of the cells as the animal is in different states of sleep.

SA: Right. We are able to go in and actually record the activity pattern of individual neurons in the brain while the animal is asleep and awake, and also as a function of what the animal has previously experienced.

What we found already is that, based on whether the animal has learned something or not–that can fundamentally change how those neurons are talking with each other, regardless of brain state, but particularly during sleep. We’re trying to understand what that dialogue, if you will, in the brain–what all of this communication in the brain–means for how you function when you wake up again.

And what you found is that during sleep, after you learn something or you experience an environment, the cells seem to speak more tightly to each other.

SA: Yeah, they seem to be more clear in terms of what they’re saying to each other, versus the scenario where you’re just passively listening to an animal who’s just going about its day-to-day, humdrum life–not experiencing anything out of the ordinary and not really learning anything new.

If an animal learns something very important for the first time and then goes to sleep, it does seem that the neurons are communicating to each other in a much more regular way, almost as if they’re trying to reinforce some sort of point by saying it over and over again, the way that we do–I know I’m guilty of this.

But they’re basically repeating themselves. They’re saying the same thing over and over again for seemingly hours. The longest that we’ve recorded this phenomenon is 24 hours, but we actually see traces of that previous experience occurring over the entire 24 hours following learning. Somehow sleep seems to be promoting that reinforcement of communication between the neurons.

The one thing that I would want people to know is you go to sleep, and you may not be conscious, and you may not recall anything that’s going on in your head, but there’s a lot going on in there. And we don’t really know what it all means. So that is still very much a mystery, as to what’s going on in the brain and what all of that communication is for.

But there’s plenty of communication going on in your brain. There’s plenty of activity. It’s not a quiet place. Your brain is actually quite busy while you’re asleep.

And then if you disturb that process like you do in your lab, then what’s the consequence for the animal once it wakes up?

SA: Well, it’s interesting. They have a type of amnesia. If you ask the animal behaviorally, “Do you remember the experience from the day before?” They behave as if they have no idea what happened. They really do behave as if they don’t remember anything, which is unusual. Normally, you would have to really disrupt activity in the brain in order to get that kind of amnesia.

And for people who unfortunately have amnesia through some kind of trauma–it usually takes a pretty traumatic event to cause amnesia–it turns out that just preventing sleep, or allowing the animal to sleep, but disrupting this pattern of activity that’s normally ongoing in fairly subtle ways, is enough to get the same kind of amnesia that you would get if you were hit upside the head, basically.

One thing I found really fascinating when I first met you a few years ago is that you told me that, in a lot of mental disorders, sleep is really affected.

SA: It’s probably one of the first things to go.

For example, dementia is one where sleep is really badly affected. Schizophrenia is one where sleep is really badly affected. Depression can be one where sleep is really adversely affected. I think in all of those disorders, where there’s a very serious cognitive component, there also tends to be a sleep component.

There’s one, Angelman Syndrome, where the parents will say of their newborn children–newborn children typically sleep 16, 18, 20 hours a day–their kids only sleep two or three hours a day.

Is it a consequence of the lack of sleep that some of these cognitive–

SA: Right, or could normalizing sleep at least indirectly have a benefit for patients who are coping with a pretty severe set of cognitive effects.

I always love listening and hearing about your research. It’s so cool and so fascinating.

SA: Same!

And I want to encourage people to go to your website and read more about what your lab is doing, and your publications are there.

SA: And if you have questions, feel free to email me. No question is too far out of left field. I love getting questions about sleep.

Yeah, it’s such an amazing topic. So before we leave today, I wanted to ask you one more question: How has being a scientist affected other parts of your life?

SA: It’s a really interesting question. So, the obvious one is just a utilitarian answer: Time!

Particularly if you’re passionate about your work, you go into lab and you just lose track of time. So the things that we all have to take care of, like laundry, eating, sleeping, bathing, family life–you know, those things can get compressed. For example, laundry is a huge one–I find myself sort of scrambling to keep up with certain things like that.

And I’m not complaining, because it’s all self-induced, and I wouldn’t have it any other way. I wouldn’t work any other job so I could have more time to devote to laundry.

But there are other ways that it sort of changes my life outside the lab, which is just that I feel like I definitely look at the world differently. I find myself applying the scientific method to political debates and things like that, which can be more or less effective, depending. Or grocery shopping. How to follow a recipe.

I get into lots of debates with my husband, who is a very strong recipe follower, where I will cut corners, because I have applied my own logic to it, and I discovered that some step is completely superfluous, with regard to the chemistry. So I will just completely ignore that, because it's the most parsimonious thing to do. And he’ll say, “What are you doing?” And I feel like it is hard to turn it off. I don’t know if the same is true for you.

Yes, my husband complains all the time that I argue.

SA: I think that takes getting used to, you know. For people around us, I feel like that takes getting used to. Because we understand social niceties, and we understand that we have to say “Okay” and move on with the conversation.

But I need data points of some sort. I need physical evidence.

I can relate to that. That’s very true. And it’s something we experience every day in the lab, and so then it’s very hard to turn it off when you go home.

SA: Yeah! Because that’s like saying there are certain rules that apply in one scenario and not in another. I mean, in our heart of hearts, I think we believe that that isn’t true–that the same rules apply everywhere.

The good thing about that is that you always question the information that’s given to you, especially in these times. We have a lot of muddled information, so it’s always good to question. But sometimes if you’re sitting at dinner, maybe question a little less so people don’t get upset about it!

SA: Yeah, questioning definitely has its utility, but questioning others, definitely in some contexts, does not have utility. So knowing the difference is something that helps us get through our day-to-day lives, but it is something that I have to check myself. And I will always be that way.

Well it was so great to talk to you. Thank you so much for sitting here with us today. And if you have questions, please email, and go check out Sara’s website. Thank you so much!

SA: Yeah, thank you!

 

 

Return to the audio for How to Science Episode 5, with scientist Sara Aton.